Biogenic silver nanoparticles eradicate of Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA) isolated from the sputum of COVID-19 patients.

In recent investigations, secondary bacterial infections were found to be strongly related to mortality in COVID-19 patients. In addition, Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA) bacteria played an important role in the series of bacterial infections that accompany infection in COVID-19. The objective of the present study was to investigate the ability of biosynthesized silver nanoparticles from strawberries (Fragaria ananassa L.) leaf extract without a chemical catalyst to inhibit Gram-negative P. aeruginosa and Gram-positive Staph aureus isolated from COVID-19 patient's sputum. A wide range of measurements was performed on the synthesized AgNPs, including UV-vis, SEM, TEM, EDX, DLS, ζ -potential, XRD, and FTIR. UV-Visible spectral showed the absorbance at the wavelength 398 nm with an increase in the color intensity of the mixture after 8 h passed at the time of preparation confirming the high stability of the FA-AgNPs in the dark at room temperature. SEM and TEM measurements confirmed AgNPs with size ranges of ∼40-∼50 nm, whereas the DLS study confirmed their average hydrodynamic size as ∼53 nm. Furthermore, Ag NPs. EDX analysis showed the presence of the following elements: oxygen (40.46%), and silver (59.54%). Biosynthesized FA-AgNPs (ζ = -17.5 ± 3.1 mV) showed concentration-dependent antimicrobial activity for 48 h in both pathogenic strains. MTT tests showed concentration-dependent and line-specific effects of FA-AgNPs on cancer MCF-7 and normal liver WRL-68 cell cultures. According to the results, synthetic FA-AgNPs obtained through an environmentally friendly biological process are inexpensive and may inhibit the growth of bacteria isolated from COVID-19 patients.

Synthesis of new 3-(4-methyl-2-arylthiazol-5-yl)-5-aryl-1,2,4-oxadiazole derivatives as potential cytotoxic and antimicrobial agents

Globally cancer is the second leading cause of death;a drug that can cure cancer with the utmost negligible side effects is still a distant goal. Due to increasing antibiotic resistance, microbial infection remains a grave global health security threat. The ongoing coronavirus pandemic increased the risk of microbial and fungal infection. A new series of 3-(4-methyl-2-arylthiazol-5-yl)-5-aryl-1,2,4-oxadiazole (7a-t) have been synthesized. The structure of synthesized compounds was confirmed by the spectrometric analysis. The newly synthesized compounds were screened for cytotoxic activity against breast cell lines MCF-7 and MDA-MB-231. Against the MCF-7 cell line compounds 7f, 7 g and 7n showed excellent activity with GI50 0.6 muM to <100 nM concentration. Compound 7b showed good activity against MDA-MB-231 cell line with GI50 47 muM. The active derivatives 7b, 7e, 7f, 7 g and 7n were further evaluated for cytotoxicity against the epithelial cell line derived from the human embryonic kidney (HEK 293) and were found nontoxic. The thiazolyl-1,2,4-oxadiazole derivatives were also screened to evaluate theirs in vitro antimicrobial potential against Escherichia coli (NCIM 2574), Proteus mirabilis (NCIM 2388), Bacillus subtilis (NCIM 2063), Staphylococcus albus (NCIM 2178), Candida albicans (NCIM 3100) and Aspergillus niger (ATCC 504). Amongst the 7a-t derivatives, six compounds 7a, 7d, 7f, 7n, 7o, 7r showed good antifungal activity against C. albicans and eight compounds 7c, 7d, 7 g, 7h, 7i, 7k, 7l and 7o showed good activity against A. niger. The potential cytotoxic and antifungal activity suggested that the thiazolyl-1,2,4-oxadiazole derivatives could assist in the development of lead compounds for the treatment of cancer and microbial infections.Copyright © 2022 The Authors

Green Synthesis of Copper Nanoparticles Using Strawberry Leaves and Study of Properties, Anti-cancer Action, and Activity Against Bacteria Isolated from Covid-19 Patients

Severe acute respiratory syndrome type 2 caused by coronavirus 2 is responsible for SARS that led to the emergence of coronavirus disease 2019 (COVID-19). Recent studies have demonstrated a high correlation between secondary bacterial infections and worse outcomes and death in COVID-19 patients. The extensive use of medicines during the last SARS-CoV epidemic led to an increase in the prevalence of multi-drug-resistant germs. Nanoparticles have important characteristics and applications in health, industry, and applied fields, etc. In medical fields, they curb and stop antibiotic-resistant diseases and pathogens. In this study, strawberry leaf extract was used to synthesize copper nanoparticles. The benefits of copper nanoparticles in inhibiting the growth of Pseudomonas aeruginosa and S. aureus bacteria isolated from COVID-19 patients' sputum were tested using the agar well diffusion method. P. aeruginosa and S. aureus bacteria play a significant part in the series of bacterial infections that arise with COVID-19 infection. (1 ml) of strawberry leaf extract was mixed with (50 ml) of copper chloride solution prepared at a concentration of 2 mM at room temperature. The mixture was blended for 7 h to produce copper nanoparticles with a concentration of 2 mM as a stock solution in an environment-friendly manner. The first indication of the production of copper nanoparticles was the increase in the color intensity of the mixture after 7 h. The nanoparticles were detected using UV spectrophotometers, and a scanning electron microscope SEM, XRD, FTIR, and UV-VIS spectral, which appeared at the absorbance of two absorptive peaks, namely: 299 and 804 nm. UV-VIS spectral examination was conducted after a month and was very intense. It also showed two absorbance peaks (300 and 805 nm) with increasing intensity. This is evidence of the insolubility of the nanomaterial and its stability over the month. The scanning electron microscopy results showed that the dimensions of the prepared copper nanoparticles ranged between (46.59 and 58.82 nm). The production of copper nanoparticles in this inexpensive and environmentally friendly biological way has given excellent results in inhibiting the growth of bacteria isolated from COVID-19 patients. The effectiveness of copper nanoparticles was tested against cancerous cells isolated from laryngeal carcinoma, called HeP-2, of a 60-year-old man. The concentration of 50% of the copper nanoparticle solution, which is equivalent to 0.5 mM, gave an inhibition rate of 44.081% in cell cultures. Its effect was compared with the sensitivity of the normal cell line of liver cells (WRL-68);the concentration of 50%, which is equivalent to 0.5 mM, gave an inhibition rate of 5.997% in cell cultures, which showed a good affinity for copper nanoparticles. From this, we conclude that the copper nanoparticles were more effective in inhibiting cancerous cell lines than the normal ones. © 2023 University of Kerbala.

Metal complexes of Tridentate Schiff base: Synthesis, Characterization, Biological Activity and Molecular Docking Studies with COVID-19 Protein Receptor.

Mononuclear chelates of Cr(III), Mn(II), Fe(III), Ni(II), Cu(II), Zn(II) and Cd(II) resulted from new tridentate Schiff base ligand, 4-((1-(5-acetyl-2,4-dihydroxyphenyl)ethylidene)amino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one, were synthesized. Metal to ligand ratio was found to be1 : 1, which was revealed via elemental analysis and characterized via various spectroscopic tools. IR has point out that the coordination of the ligand towards the metal ions was carried out via NOO donor atoms. UV-Vis, 1H NMR spectral data, molar conductivity measurements, BET surface area, melting points and theoretically through density function theory were used such as characterizing techniques in supporting further interpretation of the complexes structures. The complexes were octahedral except Cu(II) and Ni(II) complexes were tetrahedral as suggested from the magnetic moment measurement. The complexes were found to have surface area, pore volume and particle radius of 23-176 m2 g-1, 0.02-0.33 cc/g and 8.71-4.32 nm, respectively, as pointed out from BET measurement. Schiff base ligand and metal complexes were tested in vitro to estimate their antimicrobial activity opposed to Gram-negative and Gram-positive bacterial and fungal organisms. MOE 2008 was used headed for screen potential drugs with molecular docking by the protein sites of new coronavirus and the study was constructed to molecular docking without validation through MD simulations.

Synthesis of 1,2,3-Triazole-Containing 2,3-Dihydrofuran Derivatives, Evaluation of Anticancer Activity and Molecular Docking Studies

A simple and convenient one-pot three-component method to synthesize 1,2,3-triazole-based 2,3-dihydrofuran derivatives from the condensation of 5,5-dimethylcyclohexane-1,3-dione, substituted phenacyl bromide, triethylamine and 1,2,3-triazole based benzaldehyde using a mixture of CH3CN/water as a reaction medium is described. The current protocol delivers numerous advantages such as good yield, short reaction time, easy work-up and simplicity in the procedure as it uses a green method and an eco-friendly catalyst. The target compounds are screened for their in-vitro anticancer activity and most of the compounds are found to exhibit promising activity compared to standard drug Doxorubicin. Molecular docking studies performed on caspase-3 and COVID-19 main protease revealed well defined binding interactions and docking scores.

Bambusa arundinacea leaves extract-derived Ag NPs: evaluation of the photocatalytic, antioxidant, antibacterial, and anticancer activities.

Bio-fabrication has become a safe approach for silver nanoparticles (Ag NPs). The plant-mediated biosynthesized Ag NPs have emerged as a potential substitute for conventional chemical formation. The biosynthesized Ag NPs were analyzed in terms of crystalline nature, morphology, chemical composition, particle size, stability, size, and shape of the particles. The XRD, FTIR, and TEM analysis indicate the presence of the bioactive secondary metabolites compounds. The bamboo-mediated Ag NPs demonstrated a notable antibacterial efficacy against Gram-positive and Gram-negative pathogenic microorganisms and showed significant antioxidant activity against DPPH free radicals. The degradation of methylene blue at various intervals under solar light irradiation was used to evaluate the photocatalytic performance of Ag NPs. Further, Ag NPs conveyed potent anticancer activity against MCF-7 cell lines with a significant value IC50. The bamboo leaves-mediated Ag NPs synthesized Ag NPs signified strong antibacterial, antioxidant, and anticancer activity; hence, it can be used in various biomedical applications and face mask coating to prevent the coronavirus after successful clinical trials in research laboratories.

Microwave-assisted synthesis of (6-((1-(4-aminophenyl)-1H-1,2,3-triazol-4-yl)methoxy)substituted benzofuran-2-yl)(phenyl)methanones, evaluation of in vitro anticancer, antimicrobial activities and molecular docking on COVID-19

A series of 4-Aminophenyl-1H 1,2,3-traizole based benzofuran analogs were synthesized with high yields straightforwardly via microwave irradiation methods than conventional methods. The structures of synthesized compounds were confirmed based on IR, 1H, 13C NMR, and HR mass spectral analysis. All the synthesized compounds were subjected to evaluation of their in vitro anticancer activity with MCF-7, PC-3, and HeLa cell lines by MTT assay, and compounds 7m, 7j, 7e, 7g, 7b, 7h, and 7c have shown good results compared to standard Doxorubicin. Further, in vitro antimicrobial activity of synthesized compounds examined by Agar Disc Diffusion method by taking gram-positive, gram-negative bacterial, and fungal strains and turned out with encouraging results compared to standard Ciprofloxacin and Fluconazole respectively. Furthermore, molecular docking studies were carried out to find out H-bonding interactions, hydrophobic interaction with docking scores of synthesized compounds. We have carried out molecular docking on COVID-19 study with COVID-19 main protease enzyme and got outstanding binding interactions. © 2022

Rational design of an anti-cancer peptide inhibiting CD147 / Cyp A interaction.

The CD147 / Cyp A interaction is a critical pathway in cancer types and an essential factor in entering the COVID-19 virus into the host cell. Melittin acts as an inhibitory peptide in cancer types by blocking the CD147/ Cyp A interaction. The clinical application of Melittin is limited due to weak penetration into cancer cells. TAT is an arginine-rich peptide with high penetration ability into cells widely used in drug delivery systems. This study aimed to design a hybrid peptide derived from Melittin and TAT to inhibit CD147 /Cyp A interaction. An amino acid region with high anti-cancer activity in Melittin was selected based on the physicochemical properties. Based on the results, a truncated Melittin peptide with 15 amino acids by the GGGS linker was fused to a TAT peptide (nine amino acids) to increase the penetration rate into the cell. A new hybrid peptide analog(TM) was selected by replacing the glycine with serine based on random point mutation. Docking results indicated that the TM peptide acts as an inhibitory peptide with high binding energy when interacting with CD147 and the CypA proteins. RMSD and RMSF results confirmed the high stability of the TM peptide in interaction with CD147. Also, the coarse-grained simulation showed the penetration potential of TM peptide into the DOPS-DOPC model membrane. Our findings indicated that the designed multifunctional peptide could be an attractive therapeutic candidate to halter tumor types and COVID-19 infection.

Pseudanabaena galeata CCNP1313-Biological Activity and Peptides Production.

Even cyanobacteria from ecosystems of low biodiversity, such as the Baltic Sea, can constitute a rich source of bioactive metabolites. Potent toxins, enzyme inhibitors, and anticancer and antifungal agents were detected in both bloom-forming species and less commonly occurring cyanobacteria. In previous work on the Baltic Pseudanabaena galeata CCNP1313, the induction of apoptosis in the breast cancer cell line MCF-7 was documented. Here, the activity of the strain was further explored using human dermal fibroblasts, African green monkey kidney, cancer cell lines (T47D, HCT-8, and A549ACE2/TMPRSS2) and viruses (SARS-CoV-2, HCoV-OC43, and WNV). In the tests, extracts, chromatographic fractions, and the main components of the P. galeata CCNP1313 fractions were used. The LC-MS/MS analyses of the tested samples led to the detection of forty-five peptides. For fourteen of the new peptides, putative structures were proposed based on MS/MS spectra. Although the complex samples (i.e., extracts and chromatographic fractions) showed potent cytotoxic and antiviral activities, the effects of the isolated compounds were minor. The study confirmed the significance of P. galeata CCNP1313 as a source of metabolites with potent activity. It also illustrated the difficulties in assigning the observed biological effects to specific metabolites, especially when they are produced in minute amounts.

Synthesis, Characterization, Biological Activity and Molecular Docking Studies of Novel Organotin(IV) Carboxylates.

Four new carboxylates complexes with general formula R2SnL2 and R3SnL, where R = n-butyl (1, 3), methyl (2, 4) and L = 4-Chlorophenoxyacetate, were synthesized in significant yields. FT-IR analysis revealed a chelating (1 and 2) and a bridging bidentate (3 and 4) coordination modes for the carboxylate ligand in solid state which was further confirmed by the single crystal X-ray analysis of complex 4. The NMR data (1H, 13C and 119Sn) revealed a higher coordination number around the tin center in R2SnL2 (1 and 2) compared to R3SnL (3 and 4). A close matching was observed between the experimental and calculated structures (obtained at B3LYP/6-31G* + LANL2DZ basis set). Quantum chemical analysis indicates that the carboxylate moiety has the major contribution in the formation of filled and unfilled orbitals as well as in ligand to ligand intramolecular charge transfer during the electronic transitions. The cytotoxicity data of the screened compounds evaluated against lung cancer cell line (A549) and normal lung fibroblast cell line (MRC-5) revealed that 1, 3 and 4 have shown dose dependent cytotoxic effects while HL and 2 have shown steady and low cytotoxic activities. The antibacterial activity of complexes 1-4 is higher than that of HL. Molecular docking study showed an intercalation binding mode for complex 3 with DNA (docking score = -3.6005) involving four polar interactions. Complex 3 docking with tubulin (PDB ID 1SA0) with colchicine as a target protein resulted in three polar interactions (docking score -5.2957). Further, the docking analysis of the HL and 1-4 has shown an adequate interactions with the coronavirus SARS-CoV-2 spike protein, nucleocapsid protein and human angiotensin converting enzyme (ACE2).

Alkaloids and Colon Cancer: Molecular Mechanisms and Therapeutic Implications for Cell Cycle Arrest.

Cancer is the second most fatal disease worldwide, with colon cancer being the third most prevalent and fatal form of cancer in several Western countries. The risk of acquisition of resistance to chemotherapy remains a significant hurdle in the management of various types of cancer, especially colon cancer. Therefore, it is essential to develop alternative treatment modalities. Naturally occurring alkaloids have been shown to regulate various mechanistic pathways linked to cell proliferation, cell cycle, and metastasis. This review aims to shed light on the potential of alkaloids as anti-colon-cancer chemotherapy agents that can modulate or arrest the cell cycle. Preclinical investigated alkaloids have shown anti-colon cancer activities and inhibition of cancer cell proliferation via cell cycle arrest at different stages, suggesting that alkaloids may have the potential to act as anticancer molecules.

Phytochemistry and Pharmacological aspects of Tridax procumbens (L.): A Systematic and Comprehensive Review

Background Tridax procumbens L. (T. procumbens) belongs to the Asteraceae family, is an Ayurvedic herb of Asia with a history of traditional use. T. procumbens have been used from ancient times to treat wounds, skin diseases and to stop blood clotting in folk medicine. It possesses anticoagulant, antileishmanial, antioxidants, and anticancer, immunomodulatory agent, insecticidal, anthelmintic cardiovascular, antiseptic, and antimicrobial insecticidal properties. Purpose This review article aims to collate past and present updated information on traditional uses, morphology, chemical constituents and pharmacological activities, miscellaneous activities, and relevant patents of this plant, thereby providing useful data for researchers and pharmaceutical, cosmetics-related industries. Methods A review was collected from various platforms, including Science Direct, Google Scholar, Google patents, PubMed, ACS, Tayler and Francis, Mendeley Desktop databases on traditional uses, morphology, phytochemicals, pharmacological activities, and patents of T. procumbens. The literature search covers original research articles and reviews articles in peer review journals, published up to 2021 using relevant keywords. Chemical structures were drawn using Chem draw ultra 8.0. A total of 101 references were used in the present review. Results This review yielded 839 Papers. After the screening method, 101 papers were potentially discussed. Phytochemical investigation revealed more than 138 chemical compounds have been isolated or identified from T. procumbens plant covering, including 75 isolated and other identified compounds according to phytochemical analysis. This plant possesses a variety of chemical compounds including flavonoids, essential oils, saponins, and terpenoids as main secondary metabolites. Diverse pharmacological activities of T. procumbens have a wide range of bioactivities including antimicrobial, antioxidant activity, anticancer, anti-inflammatory, and wound healing properties. Toxicological knowledge is scarce at this time, and more research is needed on this plant. Conclusions T. procumbens predominantly shows wound healing, antimicrobial, anti-inflammatory properties traditionally. It is not further supported by the isolation of chemical compounds i.e. lack of bioassay-guided isolation strategies is observed. Several main active chemical compounds are present in the T. procumbens. The pharmacological effects of plant active secondary metabolites of this plant may help to defeat dangerous diseases such as diabetics, cancers, respiratory disorders like the current corona virus COVID -19 upsurge. The present treasury of traditional uses, chemical compounds, and pharmacological activities will be helpful in the future for researchers on T. procumbens in the search for new leads for drug discovery.

Antimicrobial and Anticancer Application of Silver(I) Dipeptide Complexes.

Three silver(I) dipeptide complexes [Ag(GlyGly)]n(NO3)n (AgGlyGly), [Ag2(GlyAla)(NO3)2]n (AgGlyAla) and [Ag2(HGlyAsp)(NO3)]n (AgGlyAsp) were prepared, investigated and characterized by vibrational spectroscopy (mid-IR), elemental and thermogravimetric analysis and mass spectrometry. For AgGlyGly, X-ray crystallography was also performed. Their stability in biological testing media was verified by time-dependent NMR measurements. Their in vitro antimicrobial activity was evaluated against selected pathogenic microorganisms. Moreover, the influence of silver(I) dipeptide complexes on microbial film formation was described. Further, the cytotoxicity of the complexes against selected cancer cells (BLM, MDA-MB-231, HeLa, HCT116, MCF-7 and Jurkat) and fibroblasts (BJ-5ta) using a colorimetric MTS assay was tested, and the selectivity index (SI) was identified. The mechanism of action of Ag(I) dipeptide complexes was elucidated and discussed by the study in terms of their binding affinity toward the CT DNA, the ability to cleave the DNA and the ability to influence numbers of cells within each cell cycle phase. The new silver(I) dipeptide complexes are able to bind into DNA by noncovalent interaction, and the topoisomerase I inhibition study showed that the studied complexes inhibit its activity at a concentration of 15 µM.

3-Pyridinylidene Derivatives of Chemically Modified Lupane and Ursane Triterpenes as Promising Anticancer Agents by Targeting Apoptosis.

Cancer persists as a global challenge due to the extent to which conventional anticancer therapies pose high risks counterbalanced with their therapeutic benefit. Naturally occurring substances stand as an important safer alternative source for anticancer drug development. In the current study, a series of modified lupane and ursane derivatives was subjected to in vitro screening on the NCI-60 cancer cell line panel. Compounds 6 and 7 have been identified as highly active with GI50 values ranging from 0.03 µM to 5.9 µM (compound 6) and 0.18-1.53 µM (compound 7). Thus, these two compounds were further assessed in detail in order to identify a possible antiproliferative mechanism of action. DAPI (4',6-diamidino-2-phenylindole) staining revealed that both compounds induced nuclei condensation and overall cell morphological changes consistent with apoptotic cell death. rtPCR analysis showed that both compounds induced upregulation of proapoptotic Bak and Bad genes while downregulating Bcl-XL and Bcl-2 antiapoptotic genes. Molecular docking analysis revealed that both compounds exhibited high scores for Bcl-XL inhibition, while compound 7 showed higher in silico Bcl-XL inhibition potential as compared to the native inhibitor ATB-737, suggesting that compounds may induce apoptotic cell death through targeted antiapoptotic protein inhibition, as well.

Therapeutic Potential of Thymoquinone and Its Nanoformulations in Pulmonary Injury: A Comprehensive Review.

As a crucial organ, the lung is exposed to various harmful agents that may induce inflammation and oxidative stress, which may cause chronic or acute lung injury. Nigella sativa, also known as black seed, has been widely used to treat various diseases and is one of the most extensively researched medicinal plants. Thymoquinone (TQ) is the main component of black seed volatile oil and has been proven to have antioxidant, anti-inflammatory, and antineoplastic properties. The potential therapeutic properties of TQ against various pulmonary disorders have been studied in both in vitro and in vivo studies. Furthermore, the application of nanotechnology may increase drug solubility, cellular absorption, drug release (sustained or control), and drug delivery to lung tissue target sites. As a result, fabricating TQ as nanoparticles (NPs) is a potential therapeutic approach against a variety of lung diseases. In this current review, we summarize recent findings on the efficacy of TQ and its nanotypes in lung disorders caused by immunocompromised conditions such as cancer, diabetes, gastric ulcers, and other neurodegenerative diseases. It is concluded that TQ nanoparticles with anti-inflammatory, antioxidant, antiasthma, and antitumor activity may be safely applied to treat lung disorders. However, more research is required before TQ nanoparticles can be used as pharmaceutical preparations in human studies.

Biogenic and biocompatible silver nanoparticles for an apoptotic anti-ovarian activity and as polydopamine-functionalized antibiotic carrier for an augmented antibiofilm activity.

Silver nanoparticles (AgNPs) could be employed in the combat against COVID-19, yet are associated with toxicities. In this study, biogenic and biocompatible AgNPs using the agro-waste, non-edible Hibiscus sabdariffa stem were synthesized. Under optimized reaction conditions, synthesized green AgNPs were crystalline, face cubic centered, spherical with a diameter of around 17 nm and a surface charge of -20 mV. Their murine lethal dose 50 (LD50) was 4 folds higher than the chemical AgNPs. Furthermore, they were more murine hepato- and nephro-tolerated than chemical counterparts due to activation of Nrf-2 and HO-1 pathway. They exerted an apoptotic anti-ovarian cancer activity with IC50 value 6 times more than the normal cell line. Being functionalized with polydopamine and conjugated to either moxifloxacin or gatifloxacin, the conjugates exerted an augmented antibiofilm activity against Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii biofilms that was significantly higher than antibiotic alone or functionalized AgNPs suggesting a synergistic activity. In conclusion, this study introduced a facile one-pot synthesis of biogenic and biocompatible AgNPs with preferential anti-cancer activity and could be utilized as antibiotic delivery system for a successful eradication of Gram-negative biofilms.