Pulmonary infections in cancer patients

Lymphangitis carcinomatosa refers to pulmonary interstitial involvement by cancer and is a dreaded clinical finding in oncology because it is a late manifestation indicative of metastatic malignancy, from either a lung or a nonlung primary cancer, and is associated with poor prognosis. Its presentation is nonspecific, often with subacute dyspnoea and a nonproductive cough in a person with a known history of malignancy, but in some cases is the first manifestation of cancer. CT imaging can be suggestive, typically demonstrating thickening of the peribronchovascular interstitium, interlobular septa and fissures. However, a biopsy may be required to confirm the pathological diagnosis as these changes can also be due to concurrent disease such as heart failure, ILD, infection, radiation pneumonitis and drug reactions. Diagnosis allows symptomatic treatment, with personalised treatment directed towards the primary cancer most likely to provide a meaningful benefit. Future research should focus on prospective clinical trials to identify new interventions to improve both diagnosis and treatment of lymphangitis carcinomatosa.Copyright © ERS 2021.

Synthesis, Antimicrobial, and Antibiofilm Activities of Some Novel 7-Methoxyquinoline Derivatives Bearing Sulfonamide Moiety against Urinary Tract Infection-Causing Pathogenic Microbes.

A new series of 4-((7-methoxyquinolin-4-yl) amino)-N-(substituted) benzenesulfonamide 3(a-s) was synthesized via the reaction of 4-chloro-7-methoxyquinoline 1 with various sulfa drugs. The structural elucidation was verified based on spectroscopic data analysis. All the target compounds were screened for their antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, and unicellular fungi. The results revealed that compound 3l has the highest effect on most tested bacterial and unicellular fungal strains. The highest effect of compound 3l was observed against E. coli and C. albicans with MIC = 7.812 and 31.125 µg/mL, respectively. Compounds 3c and 3d showed broad-spectrum antimicrobial activity, but the activity was lower than that of 3l. The antibiofilm activity of compound 3l was measured against different pathogenic microbes isolated from the urinary tract. Compound 3l could achieve biofilm extension at its adhesion strength. After adding 10.0 µg/mL of compound 3l, the highest percentage was 94.60% for E. coli, 91.74% for P. aeruginosa, and 98.03% for C. neoformans. Moreover, in the protein leakage assay, the quantity of cellular protein discharged from E. coli was 180.25 µg/mL after treatment with 1.0 mg/mL of compound 3l, which explains the creation of holes in the cell membrane of E. coli and proves compound 3l's antibacterial and antibiofilm properties. Additionally, in silico ADME prediction analyses of compounds 3c, 3d, and 3l revealed promising results, indicating the presence of drug-like properties.

Phytochemical Characterization and Screening of the Anti-Pneumonia (Anti-COVID-19, Anti-Fungal, and Anti-Bacterial) Activities of Cuscuta Campestris Extract

Introduction: Although, several vaccines are being approved, no effective antiviral drug has been developed for COVID-19 infectious. The present investigation was aimed to increase the essential oils of Cuscuta campestris using far-red light treatment and examine the potential of crude extracts of C. campestris against selected pneumonia pathogens and COVID-19.Methods: Anti-COVID-19 activity was determined in human lung cell lines and COVID-19 positive patients.Results: Results demonstrated that the aqueous extract had the highest amount of anti-COVID-19, antibiotic and antioxidant activity. The far-red light treatment increased Scoparone, cineole, Benzofuran, 2, 3- dihydro, Cinnamic acid, and Benzo[h]quinoline, 2, 4-dimethyl, which are mainly effective components against COVID-19 inflammation and pneumonia microbes. CT scan and clinical laboratory tests in a clinical case study, a 30-year-old woman who presented with severe 2019-nCoV, demonstrated that inhalation of 30 mg extract nebulized/day for seven days resulted in significant improvement in consolidation and ground-glass opacity in lungs on the seventh day of treatment.Conclusion: It is hoped that this study leads to the introduction of some compounds that could be used to formulate new and more potent anti-COVID-19 antibiotics, or other drugs of natural origin in medicine.

Systematic Evaluation of Studies in the Fields of Diagnosis and Management of Prostate Cancer in Coronavirus Disease 2019 Era

Background: Prostate cancer is one of the most common cancers worldwide. The proper management of this cancer during the coronavirus disease 2019 (COVID-19) or similar outbreaks could be a serious challenge. Proper timing of surgery, radiotherapy, and other medical modalities are essential in providing the most effective treatment. Objective(s): This systematic review aimed at evaluating the proper management of prostate cancer during the COVID-19 outbreak. Method(s): This study was conducted from 2019 to 2022. An internet search was conducted using the keywords: Diagnosis, man-agement, radical prostatectomy, radiotherapy, hormone ablation therapy, chemotherapy and prostate cancer, and COVID-19. The visited databases included PubMed, Scopus, Web of Sciences, Google Scholar, and Scientific Information Database. The review was performed based on the preferred reporting items for a systematic review and meta-analyses (PRISMA) guidelines. Result(s): Postponing the biopsy for up to three months and adopting of non-invasive diagnostic methods were likely reasonable during the COVID-19 pandemic. Patients with cancer were more prone to severe injuries and were more likely to have serious compli-cations. Surgery, radiation therapy, brachytherapy, palliative radiation, hormone ablation therapy, and chemotherapy were among the pre-institutional treatments that had to be performed according to medical protocols as well as health and professional guide-lines. Conclusion(s): It was recommended that the prostate cancer screening should not be performed for asymptomatic men during the COVID-19 outbreak. It was also suggested that the treatment should be performed in the shortest possible time and in the safest way.Copyright © 2023, Author(s).

Development of 2-chloroquinoline based heterocyclic frameworks as dual inhibitors of SARS-CoV-2 MPro and PLPro.

Evolution of new variants of SARS-CoV-2 warrant the need for the continued efforts in identifying target-oriented new drugs. Dual targeting agents against MPro and PLPro not only overcome the incomplete efficacy but also the drug resistance, which is common problem. Since both these are cysteine proteases, we designed 2-chloroquinoline based molecules with additional imine moiety in the middle as possible nucleophilic warheads. In the first round of design and synthesis, three molecules (C3, C4 and C5) inhibited (Ki < 2 µM) only MPro by binding covalently to C145 and one molecule (C10) inhibited both the proteases non-covalently (Ki < 2 µM) with negligible cytotoxicity. Further conversion of the imine in C10 to azetidinone (C11) improved the potency against both the enzymes in the nanomolar range (820 nM against MPro and 350 nM against PLPro) with no cytotoxicity. Conversion of imine to thiazolidinone (C12), reduced the inhibition by 3-5 folds against both the enzymes. Biochemical and computational studies suggest that C10-C12 bind in the substrate binding pocket of MPro and in the BL2 loop of the PLPro. Since these dual inhibitors have least cytotoxicity, they could be further explored as therapeutics against the SARS-CoV-2 and other analogous viruses.

A foundational theoreticalAl12E12(E = N, P) adsorption and quinolone docking study: cage-quinolone pairs, optics and possible therapeutic and diagnostic applications.

This combined Al12E12 (E = N, P) surface adsorption and docking study describes the new possibility of prospective potential probing(photophysical/optical) and therapy(medicinal/biochemical) with these adsorbent conjugates. DFT investigations were undertaken herein to help generate geometrical models and better understand the possible favorable adsorption energetics. We attempt to explain their adsorption behaviors and docking involving SARS-CoV-2 viruses (PDB)to assess their possible pharmaceutical potential against the pandemic virus (COVID-19). The adsorption behavior of 8-hydroxy-2-methylquinoline (MQ) and its halogenated derivatives, 5,7-diiodo-8-hydroxy-2-methylquinoline (MQI), 5,7-dichloro-8-hydroxy-2-methylquinoline (MQCl), and 5,7-dibromo-8-hydroxy-2-methylquinoline (MQBr), with aluminum-nitrogen (AlN), and aluminum-phosphorous (AlP) fullerene-like nanocages is reported. A decrease in the hardness of the nanoclusters when adsorbed with drug molecules resulted in an incrementally improved chemical softness (see e.g., Hard-Soft Acid Base theory) indicating that reactivity of the drug molecule in the resulting complex increases upon cluster chemical adsorption. The energy gap is found to be maximized for AlN-MQ and minimized for AlP-MQI; the reduced density gradient (RDG) iso-surfaces and AIM studies also corroborated this. Therefore, these two were found, respectively, to be the least and most electrically conductive of the species under study. We selected a simple medicinal building block (chelator)in addition to selecting the cluster based on previous literature reports. Important parameters such as gap energies and global indices were determined. We assessed NLO properties. The SARS-CoV-2 virus PDB docking data for 6VW1, 6VYO, 6WKQ, 7AD1, 7AOL, 7B3C, were enlisted as ligand targets for studies of docking (PatchDock Server) using the requisite PDB geometries (For the structure of 6VW1, kindly see reference, 2020; For the structure of 6VYO kindly see reference, 2020; For the structure of 6WKQ kindly see reference, 2020; For the structure of 7AD1 kindly see reference, 2021; For the structure of 7AOL kindly see reference, 2021; For the structure of 7B3C kindly see reference, 2021). Such findings indicate that the AlN-drug conjugation have inhibitory effect against these selected receptors.

Consumption of systemic antibiotics in the Russian Federation in 2017-2021.

Objective. To assess level and the structure of systemic antibiotic consumption in Russia over the period 2017 to 2021. Materials and methods. Data were collected and analysed in compliance with the standard protocol of the World Health Organization Regional Office for Europe by the means of ATC/DDD methodology for J01 group - antibacterials for systemic use. Consumption was calculated for outpatients and inpatients separately as a number of DDDs per 1000 inhabitants per day (DID) for the main classes of antibiotics and the agents with the highest or the most diverse consumption levels for the given period of time, and was based on the data of wholesale purchases and public tenders. Results. Antibiotic consumption in Russia in 2017, 2018, 2019, 2020, and 2021 was 16.6 DID, 14.3 DID, 14.8 DID, 19 DID, and 15.7 DID respectively. Penicillins, macrolides and lincosamides, and quinolones had the highest levels of consumption in outpatients. Prominent increase in outpatient consumption of antibacterials in 2020 was related to three agents: azithromycin, levofloxacin and ceftriaxone. Cephalosporins (mainly III-V generations), quinolones and penicillins had the highest levels of consumption in inpatients. Hospital consumption of meropenem, tigecycline, and vancomycin increased and amikacin and ciprofloxacin decreased over the duration of the study. Conclusions. Levels of systemic antibiotic consumption in Russia for the period 2017 to 2019 were relatively low and consistent with the average means for European Union and European Economic Area countries. The steep increase in consumption in 2020 was probably due to the wide use of antibiotics for the management of COVID-19 patients. The results of the study can be of value for the development of targeted national antibiotic stewardship programs and awareness campaigns as well as for the analysis of trends of emergence and spread of antibiotic resistance.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Real-life antimicrobial therapy in hospitalized patients with COVID-19 (preliminary results and recommendations).

Objective. Development of local clinical protocols for antibacterial therapy of COVID-19-associated bacterial pneumonia in the therapeutic department of the city clinical hospital based on an analysis of the treatment process in patients with COVID-19-associated pneumonia. Materials and methods. A retrospective analysis of 1382 cases of hospitalization in the therapeutic department of patients with COVID-19-associated pneumonia for the period from 2020 to 2021 was carried out. The structure of etiotropic therapy, the frequency and timing of microbiological studies of the biomaterial, the manifestations of the main markers of bacterial infection during dynamic monitoring of clinical and laboratory parameters in patients prescribed antibiotic therapy, as well as statistics of the stay of patients in the therapeutic department of the hospital were assessed. Based on the results obtained in the course of microbiological studies, an assessment was made of the microbial landscape of the lower respiratory tract of patients with an analysis of the sensitivity of strains of the leading microflora to a wide range of antibiotics. Results. The study found that the dominant flora in COVID-19-associated pneumonia in hospitalized patients was gram-negative bacteria - K. pneumoniae, P. aeruginosa and A. baumannii - their proportion was more than 50%. Among K. pneumoniae strains, 89.4% were ESBL producers, 63.5% of the strains were resistant to carbapenems, which with a high probability allows them to be considered carbapenemase-producing strains. Among the strains of P. aeruginosa, the proportion of strains resistant to carbapenems and with a high degree of probability being strains - producers of carbapenemase was 41.1%. Among strains of Acinetobacter spp. these were 76.4%, and associated resistance to fluoroquinolones and aminoglycosides was also demonstrated. Gram-positive microorganisms were found in 34.3% of cases and were mainly represented by strains of S. aureus (74.9%), only 26.4% of strains of this pathogen were methicillin-resistant. Conclusions. Microbiological monitoring conducted in 2020-2021 revealed the presence, among the pathogens of viral-bacterial pneumonia, at an early stage of hospitalization, a significant proportion of gram-negative bacteria with resistance of the MDR and XDR types. Based on the obtained microbiological data, starting empirical schemes for antibacterial therapy of secondary viral and bacterial pneumonia, which complicated the course of a new coronavirus infection COVID-19 caused by the SARS-CoV-2 virus, were developed and proposed.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

A quinoline-benzotriazole derivative: Synthesis, crystal structure and characterization by using spectroscopic, DFT and molecular docking methods

In this research, FT-IR, NMR (1H & 13C), mass spectrometry and single-crystal X-ray diffraction has been used to characterize the synthesized 5-((1H-benzo[d][1,2,3]triazol-1-yl)methyl)quinolin-8-ol (DD2) derivative. B3LYP calculations with the 6-31G* and 6–311++G** basis sets have shown that the most stable C2 structure in gas phase and aqueous solution is in agreement with the experimental determined by X-ray diffraction. Higher dipole moments for C2 in aqueous solution, predicted with both methods, are probably related to its higher stability resulting higher volume contraction (ΔV −1.0 Å3) in solution with the B3LYP/6-31G* method. Similar behaviours in the Mulliken and NPA charges but different from MK charges are observed. Bond orders studies reveal that the O15-H16···N17 bonds are present in both media, as was experimentally observed in the solid state. MEP surfaces have evidenced nucleophilic sites on N of triazol ring while weak electrophilic ones on aromatic H of three rings being the H atom of OH the most labile. Gap values support a lower reactivity of C2 in solution, in agreement with the higher stability evidenced by AIM analyses. The higher electronic density on triazol ring could justify that C2 is unstable in solution, as revealed by NBO analyses. Complete assignments of 93 expected vibration normal modes of C2 and a set of scaled force constants were obtained in both media by using harmonic force fields. Comparisons between experimental and theoretical infrared and 1H- and 13C NMR spectra show reasonable concordances. Intermolecular interactions in the crystal packing of DD2 were studied by using Hirshfeld surface analysis. Furthermore, DD2 was investigated against two targets of SARS-CoV-2 (PDB ID: 6WCF and PDB ID: 6Y84) by using molecular docking studies. Finally, drug likeness and ADME properties of DD2 were researched and compared with hydroxychloroquine, remdesivir, oseltamivir, lopinavir, ritonavir molecules associated as SARS-CoV-2 inhibitors. © 2023 The Authors

Clinico-Epidemiological Profile of Cutaneous Adverse Drug Reactions at Rural Tertiary Care Centre

Background: Cutaneous adverse drug reactions (CADRs), also known as toxidermia, are skin manifestations resulting from systemic drug administration and it constituted 10%-30% among all reported adverse drug reactions (ADRs). These reactions range from mild morbilliform drug rash to much more severe reactions. Material(s) and Method(s): A retrospective observational study was conducted at dermatology outpatient department of rural based tertiary care center for a duration of 03 years from August 2019 to July 2022, a total of 211 patients who had been clinically diagnosed or were suspected to have drug reactions were studied. Result(s): In this observation there was male preponderance (59.72%) and majority of patients were in their 3rd and 4th decade (40.28%) with maculopapular drug rash (33.17%) being most common clinical profile of CADRs, followed by urticaria (23.70%). Less frequently seen CADRs were acneiform eruptions (21), hair Loss (9), photodermatitis (9), generalised pruritus (7), erythroderma (2), pityriasis rosea (2), Stevens Johnson Syndrome-Toxic Epidermal Necrolysis (SJS-TEN) (4), lichenoid drug eruptions (3), Vasculitis (1) and pustular drug eruption (1). The most common group of drugs causing CADRs were antibiotics (40.28%), followed by NSAIDs (28.43%). Conclusion(s): Cutaneous Adverse Drug Reactions (CADRs) are price we pay for the benefits of modern drug therapy;knowledge of these reactions is important for treating physician as prompt recognition and treatment can prove lifesaving.Copyright © 2022 Academic Medicine and Pharmacy

Emerging quinoline- and quinolone-based antibiotics in the light of epidemics.

Pandemics are large-scale outbreaks of infectious disease that can greatly increase morbidity and mortality all the globe. Since past 1990 till twentieth century, these infectious diseases have been major threat all over the globe associated with poor hygiene and sanitation. In light of these epidemics, researches have gained enormous rise in the developing the potential therapeutic treatment. Thus, revolutionized antibiotics have led to the near eradication of such ailments. Around 50 million prescription of antibiotics written in US per year according to center for disease control and prevention (CDC) report. There is a wide range of antibiotics available which differ in their usage and their mechanism of action. Among these quinoline and quinolone class of antibiotics get attention as they show tremendous potential in fighting the epidemics. Quinoline and quinolone comprise of two rings along with substitutions at different positions which is synthetically obtained by structural modifications of quinine. Quinoline and quinolone antibiotics exhibit extensive activities approved by FDA in the treatment of the several ailments such as gastrointestinal infections, urinary tract infections, prostate inflammation, malaria, gonorrhea, skin infection, colorectal cancer, respiratory tract infections. These are active against both gram-negative and gram-positive bacteria. This basic core of quinoline and quinolone is vital due to its capability of targeting the pathogen causing disease and beneficial in treating the infectious disease. They inhibit the synthesis of nucleic acid of bacteria which results in the rupture of bacterial chromosome due to the interruption of enzymes such as DNA gyrase and topoisomerase IV. There are various quinoline and quinolone compounds that are synthetically derived by applying different synthesis approaches which show a wide range of pharmacological activities in several diseases. The most commonly used are fluoro, chloro, and hydroxychloro derivatives of quinoline and quinolone. These compounds are helpful in the treatment of numerous epidemics as a chief and combination therapy. These quinoline and quinolone pharmacophore fascinate the interest of researchers as they inhibit the entry of virus in host cell and cease its replication by blocking the host receptor glycosylation and proteolytic processing. They act as immune modulator by inhibiting autophagy and reduction of both lysosomal activity and production of cytokine. Therefore, quinoline and quinolone derivatives attain significance in area of research and treatment of various life-threatening epidemics such as SARS, Zika virus, Ebola virus, dengue, and COVID-19 (currently). In this chapter, the research and advancements of quinoline- and quinolone-based antibiotics in epidemic management are briefly discussed.

Structural Insight into 2-Aryl-4-Quinoline Carboxylic Acid-Based Dihydroorotate Dehydrogenase (DHODH) and its Potential Anti-SARS-CoV-2 Activity Through Pharmacophore Modeling, Multidimensional QSAR, ADME, and Docking Studies

Dihydroorotate dehydrogenase (DHODH) is a rate-limiting enzyme in the biosynthesis of pyrimidine, which catalyzes the oxidation of dihydroorotate to orotate. Uridine monophosphate is biosynthesized by orotate. DHODH inhibitors have been shown to have antiviral activity against cytomegalovirus, Ebola, influenza, Epstein-Barr virus, and picornavirus. The anti-SARS-CoV-2 activity of DHODH inhibitors has also been investigated. DHODH inhibitors, including leflunomide and its metabolite teriflunomide, have been found to have anti-SARSCoV-2 activity. In relation to the importance of this enzyme (i.e., DHODH) in drug design, the present study aimed to develop statistically robust and interpretable 2D and 3D-quantitative structure-activity relationship (QSAR) models based on a dataset of 92 molecules of biologically active 2-aryl-4-quinoline carboxylic acid analogs, reported as DHODH inhibitors. The correlation coefficient (R2) values of the training set of the partial least squares (PLS) and all five Kernel-based PLS models for the respective fingerprints were found to be 0.7091, 0.8336 (linear), 0.7586 (radial), 0.8606 (dendritic), 0.6832 (desc), and 0.7670 (Molprint 2D), respectively (R2 ≈ 0.9). However, the external validation coefficient (Q2) values of the test set were found to be 0.7009, 0.7503 (linear), 0.7737 (radial), 0.8250 (dendritic), 0.6756 (desc), and 0.7533 (Molprint 2D), respectively (Q2 > 0.6). The developed 4-point pharmacophore model (ARRR_1), with one hydrogen bond acceptor and three aromatic rings, was found to be crucial in preserving the activity of 2-aryl-4-quinoline carboxylic acid analogs as DHODH inhibitors. Furthermore, the molecular docking of DHODH inhibitors against SARS-CoV-2 target proteins revealed the significant role of DHODH inhibitors. © 2023, Physical Chemistry Research. All Rights Reserved.

Synthesis of Potential Antiviral Agents for SARS-CoV-2 Using Molecular Hybridization Approach.

We synthesized a set of small molecules using a molecular hybridization approach with good yields. The antiviral properties of the synthesized conjugates against the SAR-CoV-2 virus were investigated and their cytotoxicity was also determined. Among all the synthesized conjugates, compound 9f showed potential against SARS-CoV-2 and low cytotoxicity. The conjugates' selectivity indexes (SIs) were determined to correlate the antiviral properties and cytotoxicity. The observed biological data were further validated using computational studies.

Synthesis, spectral characterization, crystal structure and computational investigation of 2-formyl-6-methoxy-3-carbethoxy quinoline as potential SARS-CoV inhibitor.

The recent COVID-19 outbreak caused by the novel coronavirus SARS-CoV-2 has an immense impact on global health and economy. Although vaccines are being used, urgent need of drugs based on natural products with high efficacy and safety is a pressing priority. Quinoline alkaloids are well known for their therapeutic action against malaria; initially, it was tried against Coronaviruses. It is a basic vital scaffold to design drugs with required biological and pharmacological activities. In this present study, a new quinoline compound was synthesized and characterized by spectroscopy techniques. Crystal structure was established by SCXRD analysis and data is used as an input to perform various computations. Additionally, using state-of-the-art quantum computational techniques, the geometry optimization and calculation of UV-Vis spectrum of 2F6M3CQ were performed at B3LYP/6-311G* level of theory. The optimized molecular geometric parameters as well as UV-Vis spectrum values are found to be in good agreement with their respective experimental results. The visualization of 3-D plots of FMO and MEP indicated the structure and reactivity trends of 2F6M3CQ molecule. Molecular docking methods were utilized to find the drug ability of 2F6M3CQ with Mproprotein of SARS-CoV-2. There were many intermolecular interactions between Mpro protein and 2F6M3CQ molecule which lead to good binding energy (-5.5 kcal/mol) between them which was found to be better than the binding energy of chloroquinine molecule (-4.5 kcal/mol) as studied under same docking protocols. Finally, drug likeness and ADME properties of 2F6M3CQ were also analyzed. There is no violation found for RO5 in our 2F6M3CQ compound. ADME analysis shows drug like properties of compound 2F6M3CQ which predicts that it might be a potential candidate for inhibition of SARS-CoV-2.

Synthesis of New 1,2,3,4-Tetrahydroquinoline Hybrid of Ibuprofen and Its Biological Evaluation

Herein we report the obtaining of 1-(3,4-dihydroquinolin-1(2H)-yl)-2- (4-isobutylphenyl)propan-1-one and its characterization. The newly obtained hybrid and its derivatives (hybrids of ibuprofen with 1,2,3,4-tetrahydroisoquinoline, and piperidine) were screened for their in vitro antioxidant, antitryptic, and inhibition of albumin denaturation activity. The lipophilicity was established using both reversed-phase thin layer chromatography and in silico calculations.

Quinoline heterocyclic containing plant and marine candidates against drug-resistant Mycobacterium tuberculosis: A systematic drug-ability investigation.

Today, tuberculosis (TB) caused by the acid-fast bacilli, Mycobacterium tuberculosis (Mtb) is the most infectious killer disease globally with high morbidity and mortality rates. The rapid development of multi-drug-resistant (MDR) strains via intrinsic (efflux pumps) and acquired (biological mutations) mechanisms reduce the efficacy of applied anti-TB regimens. Nevertheless, only bedaquiline (BDQ) and pretomanid (PMD) were added to anti-TB therapy in the last decade. The existing anti-TB drugs also exhibited cytotoxicity and hepatotoxicity from long-term treatment. Thus, exploring or developing potential and less toxic anti-TB candidates, preferably natural-based candidates, is the call of the day. At present, 'quinoline' could be considered one of the versatile scaffolds presented in most mainstream medicines from comprehensive drug reports. Notably, BDQ with two clinically evaluating anti-TB candidates, TBJA-587 and DC-159a was motivated for utilizing quinoline heterocycles. Accordingly, we have selected 65 natural quinoline heterocycles bearing potential anti-TB agents (40 plant-derived and 25 marine-derived) within MIC value ≤ 50 µg/mL from an extensive literature search. Briefly, source, drug chemistry, structural activity relationship, prior pharmacokinetics profiles with drug-ability, toxicity, and hierarchical clustering analysis using various computational tools to identify the most 'drug-able lead' candidate is the uniqueness of the review. From extensive drug analysis, tetrandrine, 2'-nortiliacorinine, tiliacorine, globospiramine, evocarpine, allocuspareine from plant sources, and ecteinascidin 770, 6-hydroxymanzamine E, (-)-8-hydroxymanzamine A, ecteinascidin 786, manzamine F from marine sources are the most potential-cum-drug-able anti-TB candidates. We hope the systematic and critical drug analyses on quinoline-bearing natural anti-TB candidates are helpful to design potential-cum-less toxic anti-TB drugs in the future.

Computational Screening of Phenylamino-Phenoxy-Quinoline Derivatives against the Main Protease of SARS-CoV-2 Using Molecular Docking and the ONIOM Method.

In the search for new anti-HIV-1 agents, two forms of phenylamino-phenoxy-quinoline derivatives have been synthesized, namely, 2-phenylamino-4-phenoxy-quinoline and 6-phenylamino-4-phenoxy-quinoline. In this study, the binding interactions of phenylamino-phenoxy-quinoline derivatives and six commercially available drugs (hydroxychloroquine, ritonavir, remdesivir, S-217622, N3, and PF-07321332) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) were investigated using molecular docking and the ONIOM method. The molecular docking showed the hydrogen bonding and hydrophobic interactions of all the compounds in the pocket of SARS-CoV-2 main protease (Mpro), which plays an important role for the division and proliferation of the virus into the cell. The binding free energy values between the ligands and Mpro ranged from -7.06 to -10.61 kcal/mol. The molecular docking and ONIOM results suggested that 4-(2',6'-dimethyl-4'-cyanophenoxy)-2-(4″-cyanophenyl)-aminoquinoline and 4-(4'-cyanophenoxy)-2-(4″-cyanophenyl)-aminoquinoline have low binding energy values and appropriate molecular properties; moreover, both compounds could bind to Mpro via hydrogen bonding and Pi-Pi stacking interactions with amino acid residues, namely, HIS41, GLU166, and GLN192. These amino acids are related to the proteolytic cleavage process of the catalytic triad mechanisms. Therefore, this study provides important information for further studies on synthetic quinoline derivatives as antiviral candidates in the treatment of SARS-CoV-2.

Front Cover: Anti-SARS-CoV-2 Inhibitory Profile of New Quinoline Compounds in Cell Culture-Based Infection Models (Chem. Eur. J. 4/2022)

A new anti-SARS-CoV-2 compound, developed in this joint study, is shown in front of SARS-CoV-2 viruses. The ongoing pandemic of human SARS-CoV-2 infections (COVID-19) creates a high demand for antiviral drug development. The shown quinoline?morpholine hybrid and other new quinoline-based compounds were synthesized and investigated for their in vitro activity against SARS-CoV-2. They exerted an anti-SARS-CoV-2 activity similar to or stronger than that of the reference drug. More information can be found in the Research Article by M. Marschall, S.?B. Tsogoeva et?al. (DOI: 10.1002/chem.202103861).

Newly Identified COVID-19 Drug Candidates Based on Computational Strategies

The COVID-19 has raised a public health catastrophe in early 2020 worldwide. Despite several approved vaccines that have repressed the pandemic and decreased the mortality rate since then, attempts to discover an effective antiviral drug have not indicated reliable results. In this research, in silico studies (virtual screening and molecular docking) were performed based on quinoline structure to identify novel drug candidates against SARS-CoV-2 before laboratory evaluations. A chemical library consisting of 548 compounds was collected from literature mining of five databases to select the best ligands interacting with three target proteins of SARS-CoV-2, including the main protease, spike protein, and chimeric receptor-binding domain in a complex of human angiotensin-converting enzyme 2. The top five compounds that presented suitable binding energy against each target protein are reported in detail for the first time. Notably, new compound N-4-(6-methyl-3-pyridinyl) phenyl)-9-acridinamine showed high affinity to all selected proteins. These identified compounds will help in speeding up the drug development against COVID-19. [ FROM AUTHOR] Copyright of Journal of Computational Biophysics & Chemistry is the property of World Scientific Publishing Company and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Anthranilamides with quinoline and ß-carboline scaffolds: design, synthesis, and biological activity.

In the present study, we report the design and synthesis of novel amide-type hybrid molecules based on anthranilic acid and quinoline or ß-carboline heterocyclic scaffolds. Three types of biological screenings were performed: (i) in vitro antiproliferative screening against a panel of solid tumor and leukemia cell lines, (ii) antiviral screening against several RNA viruses, and (iii) anti-quorum sensing screening using gram-negative Chromobacterium violaceum as the reporter strain. Antiproliferative screening revealed a high activity of several compounds. Anthranilamides 12 and 13 with chloroquine core and halogenated anthranilic acid were the most active agents toward diverse cancer cell lines such as glioblastoma, pancreatic adenocarcinoma, colorectal carcinoma, lung carcinoma, acute lymphoblastic, acute myeloid, chronic myeloid leukemia, and non-Hodgkin lymphoma, but also against noncancerous cell lines. Boc-protected analogs 2 and 3 showed moderate activities against the tested cancer cells without toxic effects against noncancerous cells. A nonhalogenated quinoline derivative 10 with N-benzylanthranilic acid residue was equally active as 12 and 13 and selective toward tumor cells. Chloroquine and quinoline anthranilamides 10-13 exerted pronounced antiviral effect against human coronaviruses 229E and OC43, whereas 12 and 13 against coronavirus OC43 (EC50 values in low micromolar range; selectivity indices from 4.6 to > 10.4). Anthranilamides 14 and 16 with PQ core inhibited HIV-1 with EC50 values of 9.3 and 14.1 µM, respectively. Compound 13 displayed significant anti-quorum/biofilm effect against the quorum sensing reporter strain (IC50 of 3.7 µM) with no apparent bactericidal effect.