Biocatalytic approach for the synthesis of chiral alcohols for the development of pharmaceutical intermediates and other industrial applications: A review.

Biocatalysis has emerged as a strong tool for the synthesis of active pharmaceutical ingredients (APIs). In the early twentieth century, whole cell biocatalysis was used to develop the first industrial biocatalytic processes, and the precise work of enzymes was unknown. Biocatalysis has evolved over the years into an essential tool for modern, cost-effective, and sustainable pharmaceutical manufacturing. Meanwhile, advances in directed evolution enable the rapid production of process-stable enzymes with broad substrate scope and high selectivity. Large-scale synthetic pathways incorporating biocatalytic critical steps towards >130 APIs of authorized pharmaceuticals and drug prospects are compared in terms of steps, reaction conditions, and scale with the corresponding chemical procedures. This review is designed on the functional group developed during the reaction forming alcohol functional groups. Some important biocatalyst sources, techniques, and challenges are described. A few APIs and their utilization in pharmaceutical drugs are explained here in this review. Biocatalysis has provided shorter, more efficient, and more sustainable alternative pathways toward existing small molecule APIs. Furthermore, non-pharmaceutical applications of biocatalysts are also mentioned and discussed. Finally, this review includes the future outlook and challenges of biocatalysis. In conclusion, Further research and development of promising enzymes are required before they can be used in industry.

Effect of thymol on properties of bionanocomposites from poly (lactic acid)/poly (butylene succinate)/nanofibrillated cellulose for food packaging application.

The present study developed the formulation of active bionanocomposites films endowed with the abilities of high biodegradability and antimicrobials for active packaging applications. The aim of this work was to prepare poly (lactic acid)/poly (butylene succinate) (PLA/PBS) blended films reinforced with different concentrations of nanofibrillated cellulose (NFC) and 9 % of thymol essential oil (EO) using the casting method. The active films were further evaluated through Fourier transform infrared spectroscopy (FTIR); as well as mechanical, physical, water vapour permeability (WVP), thermal analysis (TGA), biodegradation, morphological, and antimicrobial (% reduction of bacteria) testing. The tensile strength (TS) of PLA/PBS blend films increased by 12 % with the incorporation of 2 wt% of NFC. The PLA/PBS/NFC with 9 % thymol EO has a good water barrier performance with its tensile strength, elongation at break, and tensile modulus was 13.2 MPa, 13.1 %, and 513 MPa respectively. The presence of NFC promoted the disintegration of PLA/PBS films by 70.5 %. These films promoted the antibacterial activity against S. aureus and E. coli. The study demonstrates that the developed films improved the qualities of chicken fillets and have great potential to be used as active bionanocomposites in food packaging applications.

An Updated and Focused Review on Heterocyclic Inhibitors for SARSCoV and SARS-CoV-2 3CLpro.

BACKGROUND: SARS-CoV and SARS-CoV-2 are exceedingly contagious and typically result in major respiratory illnesses (acute respiratory syndrome). The public health is facing enormous challenges across all the nations due to these newly emerging pathogens. Reliable and systematic examination of SARS-CoV and COVID-19 will assist in identifying infectious persons accurately. Based on the biological, chemical, and genetic link of SARS CoV-2 towards SARS-CoV, the recurrence of different anti-SARS-CoV natural drug molecules may be beneficial in the advancement of anti-COVID-19 herbal drug molecules. Here in this review, we evaluated SAR research that has recently been published as well as molecular docking analysis of previously synthesised compounds that have been targeted against SARS-CoV and SARS-CoV-2, respectively. This investigation might assist scientists in creating novel and revolutionary molecules that could target SAR-CoV-2. OBJECTIVES: The review highlights the heterocyclic inhibitors' ability to successfully inhibit SARSCoV and SARS-CoV-2. The meticulously described structure-activity relationship of potential SARS-CoV and SARS-CoV-2 inhibiting compounds has been addressed in this review. EVIDENCE ACQUISITION: We conducted a thorough literature assessment employing electronic databases for scientific articles highlighting potential heterocyclic inhibitors for SARS-CoVand SARSCoV- 2, published from 2010 to 2021. We recovered 415 articles, but only 220 were involved and conversed in this manuscript. The article apprehended appropriate research considering three areas: 1) SAR activity, 2) Molecular docking, and 3) Biological activity and future prospects on SARS-CoV-2. METHODS: The potential compounds with decent inhibitory activity have been discussed and reviewed along with their inhibition potential, expressed in terms of IC50 value. RESULTS: Heterocyclic scaffolds reflect an extensive spectrum of therapeutic activity and might function as an initiating concept for the designing and discovery of potential inhibitors for SARS-CoV and SARS-CoV-2 treatment. CONCLUSION: The points highlighted here may prove to be a vital tool for medicinal chemists working/ investigating more potent and efficacious scaffolds in treating SARS-CoV and SARS-CoV-2.

Recent Advancement in Drug Design and Discovery of Pyrazole Biomolecules as Cancer and Inflammation Therapeutics.

Pyrazole, an important pharmacophore and a privileged scaffold of immense significance, is a five-membered heterocyclic moiety with an extensive therapeutic profile, viz., anti-inflammatory, anti-microbial, anti-anxiety, anticancer, analgesic, antipyretic, etc. Due to the expansion of pyrazolecent red pharmacological molecules at a quicker pace, there is an urgent need to put emphasis on recent literature with hitherto available information to recognize the status of this scaffold for pharmaceutical research. The reported potential pyrazole-containing compounds are highlighted in the manuscript for the treatment of cancer and inflammation, and the results are mentioned in % inhibition of inflammation, % growth inhibition, IC50, etc. Pyrazole is an important heterocyclic moiety with a strong pharmacological profile, which may act as an important pharmacophore for the drug discovery process. In the struggle to cultivate suitable anti-inflammatory and anticancer agents, chemists have now focused on pyrazole biomolecules. This review conceals the recent expansion of pyrazole biomolecules as anti-inflammatory and anticancer agents with an aim to provide better correlation among different research going around the world.

How Internet Websites Portray Herbal Vitality Products Containing Eurycoma longifolia Jack: An Evaluation of the Quality and Risks of Online Information.

BACKGROUND: Tongkat Ali (TA) or Eurycoma longifolia is a herbal medicine (HM) plant traditionally used to treat sexual dysfunction and enhance libido in men. Websites containing information about HM are abundant. However, studies have shown that in general the quality of websites containing information on HM is low. The present study aims to assess the quality and risks of websites containing information about TA supplements and to identify the health claims for TA. METHODOLOGY: A cross-sectional study to evaluate the quality and risks of websites discussing TA supplements was conducted. Online marketing websites, research articles, news articles, personal opinions, and those restricted by password were excluded. The quality and risks of websites were assessed using a modified DISCERN tool and a set of risk assessment criteria, respectively. The health claims for TA were identified and analyzed using content analysis. RESULTS: Overall, 321 websites met the inclusion criteria and were further evaluated. The overall rating of the quality of the websites was low, with a mean score ± standard deviation of 1.07 ± 0.51. Most websites lacked information that there may be more than one possible treatment choice and did not discuss areas of uncertainty. However, 67.9% (218/321) of the websites received a risk score of zero. A minority of websites (5/321, 1.6%) discouraged the use of conventional medicines. The most common health claims for TA included in the websites related to the enhancement of testosterone level (121/321, 37.7%), treatment of malaria (112/321, 34.9%), and improvement in libido (108/321, 33.6%). CONCLUSIONS: Websites containing information about TA supplements generally have a low-quality rating based on a modified DISCERN tool despite having a low-risk score. Government agencies and healthcare professionals (HCPs) must be more proactive in the critique and dissemination of information relating to HM, and in ensuring the safe use of HM among the public and patients.

Recent Advancements in CNS Acting Drugs: A Step Towards End of Illness.

Progressive degeneration in the morphology and functions of neuronal cells leads to multifactorial pathogenesis conditions of oxidative stress, mitochondrial dysfunction, excitotoxicity, nitric oxide toxicity, and neuro-inflammation to mediate heterogeneous types of neurodegenerative diseases, such as Epilepsy, Alzheimer's (AD) and Parkinson's (PD), more prominently among aging populations. In this editorial, complex mechanisms, challenges, and advancements made in the discovery of new neurotherapeutics, as well as designing approaches being adopted to fabricate brain-targeted delivery systems, are discussed.

Withdrawn: Biomarkers in Disease Diagnosis and the Role of LC-MS and NMR: A Review

The article has been withdrawn at the request of the editor of the journal Current Pharmaceutical Design.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication. ©

Design, Synthesis, Molecular Docking, and Biological Evaluation of Pyrazole Hybrid Chalcone Conjugates as Potential Anticancer Agents and Tubulin Polymerization Inhibitors.

Some (E)-3-(3-(4-(benzyloxy)phenyl)-1-phenyl-1H-pyrazol-4-yl)-1-phenylprop-2-en-1-one conjugates 5a-r were designed; synthesized; characterized by 1H, 13C NMR, and ESI-MS; and evaluated for tubulin polymerization inhibitory activity and in vitro cytotoxicity against breast (MCF-7), cervical (SiHa), and prostate (PC-3) cancer cell lines, as well as a normal cell line (HEK-293T). The compounds were also tested to determine their binding modes at the colchicine-binding site of tubulin protein (PDB ID-3E22), for in silico ADME prediction, for bioactivity study, and for PASS prediction studies. Among all the synthesized conjugates, compound 5o exhibited excellent cytotoxicity with an IC50 value of 2.13 ± 0.80 µM (MCF-7), 4.34 ± 0.98 µM (SiHa), and 4.46 ± 0.53 µM (PC-3) against cancer cell lines. The compound did not exhibit significant toxicity to the HEK cells. Results of the in silico prediction revealed that the majority of the conjugates possessed drug-like properties.

Overview of Chemistry and Therapeutic Potential of Non-Nitrogen Heterocyclics as Anticonvulsant Agents.

Epilepsy is a chronic neurological disorder, characterized by the predisposition of unprovoked seizures affecting the neurobiological, psychological, cognitive, economic, and social wellbeing of the patient. As per the 2019 report by World Health Organization, it affects nearly 80% of the population, which comes from middle to low-income countries. It has been suggested that 70% of such cases can be treated effectively if properly diagnosed. It is one of the most common neurological diseases affecting 50 million people globally. Most of the antiepileptic drugs used in clinical practice are only 60-80% effective in controlling the disease. These drugs suffer from serious drawbacks of non-selectivity and toxicity that limit their clinical usefulness. Hence, there is a need to search for safe, potent, and effective anti-epileptic drugs. One of the emerging strategies to discover and develop selective and non-toxic anticonvulsant molecules focuses on the design of non-nitrogen heterocyclic compounds (NNHC). Drugs such as valproic acid, gabapentin, viagabatrin, fluorofelbamate, tiagabine, progabide, pregabalin, gamma amino butyric acid (GABA), etc. do not contain a nitrogen heterocyclic ring but are as effective anticonvulsants as conventional heterocyclic nitrogen compounds. This review covers the various classes of NNHC which have been developed in the recent past as anticonvulsants along with their chemistry, percentage yield, structure-activity relationship and biological activity. The most potent compound in each series has been identified for comparative studies, for further structural modification and to improve the pharmacokinetic profile. Various optimized synthetic pathways and diverse functionalities other than nitrogen-containing rings discussed in the article may help medicinal chemists to design safe and effective anticonvulsant drugs in near future.

Current Status of Novel Pyridine Fused Derivatives as Anticancer Agents: An Insight into Future Perspectives and Structure Activity Relationship (SAR).

Cancer is a heterogeneous disease characterized by an abnormal and uncontrolled division of the cells leading to tumors that invade the adjacent normal tissues. After cardiovascular diseases, it is the second most prevalent disease accounting for one in every six deaths worldwide. This alarming rate thus, demands an urgent need to investigate more effective drugs to combat the said disease. Oxygen and nitrogen-based heterocyclic compounds have shown remarkable therapeutic activity towards several diseases, including cancer. In this review, we have attempted to summarize the work done in the last decade (2009-2019), highlighting the anticancer activity of pyrido fused fivemembered heterocyclic ring derivatives. Additionally, we have focused on seven heterocyclic pyridine fused rings: Imidazopyridine, Triazolopyridine, Pyrrolopyridine, Pyrazolopyridines, Thienopyridine, and Isoxazolopyridine. A total of forty-nine compounds have been studied based on their invitro cytotoxic activity and their structure-activity relationship, underlining the anticancer activity of their various pharmacophores and substituents. This review, therefore, aims to draw the attention of the researchers worldwide towards the enormous scope of development of heterocyclic drug compounds, focussing mainly on pyrido fused five-membered heterocyclic rings as anticancer drugs.

GPR119 agonists: Novel therapeutic agents for type 2 diabetes mellitus.

Diabetes mellitus type 2 (T2D) is a group of genetically heterogeneous metabolic disorders whose frequency has gradually risen worldwide. Diabetes mellitus Type 2 (T2D) has started to achieve a pandemic level, and it is estimated that within the next decade, cases of diabetes might get double due to increase in aging population. Diabetes is rightly called the 'silent killer' because it has emerged to be one of the major causes, leading to renal failure, loss of vision; besides cardiac arrest in India. Thus, a clinical requirement for the oral drug molecules monitoring glucose homeostasis appears to be unmet. GPR119 agonist, a family of G-protein coupled receptors, usually noticed in ß-cells of pancreatic as well as intestinal L cells, drew considerable interest for type 2 diabetes mellitus (T2D). GPR119 monitors physiological mechanisms that enhance homeostasis of glucose, such as glucose-like peptide-1, gastrointestinal incretin hormone levels, pancreatic beta cell-dependent insulin secretion and glucose-dependent insulinotropic peptide (GIP). In this manuscript, we have reviewed the work done in the last five years (2015-2020) which gives an approach to design, synthesize, evaluate and study the structural activity relationship of novel GPR119 agonist-based lead compounds. Our article would help the researchers and guide their endeavours in the direction of strategy and development of innovative, effective GPR119 agonist-based compounds for the management of diabetes mellitus type 2.

Design, Synthesis, Molecular Docking, and Anticancer Evaluation of Pyrazole Linked Pyrazoline Derivatives with Carbothioamide Tail as EGFR Kinase Inhibitors.

BACKGROUND: The Epidermal Growth Factor Receptor (known as EGFR) induces cell differentiation and proliferation upon activation through the binding of its ligands. Since EGFR is thought to be involved in the development of cancer, the identification of new target inhibitors is the most viable approach, which recently gained momentum as a potential anticancer therapy. OBJECTIVE: To assess various pyrazole linked pyrazoline derivatives with carbothioamide for EGFR kinase inhibitory as well as anti-proliferative activity against human cancer cell lines viz. A549 (non-small cell lung tumor), MCF-7 (breast cancer cell line), SiHa (cancerous tissues of the cervix uteri), and HCT-116 (colon cancer cell line). METHODS: In vitro EGFR kinase assay, in vitro MTT assay, Lactate dehydrogenase release, nuclear staining (DAPI), and flow cytometry cell analysis. RESULTS: Compounds 6h and 6j inhibited EGFR kinase at concentrations of 1.66µM and 1.9µM, respectively. Furthermore, compounds 6h and 6j showed the most potent anti-proliferative results against the A549 KRAS mutation cell line (IC50 = 9.3 & 10.2µM). Through DAPI staining and phase contrast microscopy, it was established that compounds 6h and 6j also induced apoptotic activity in A549 cells. This activity was further confirmed by FACS using Annexin-V-FITC and Propidium Iodide (PI) labeling. Molecular docking studies performed on 6h and 6j suggested that the compounds can bind to the hinge region of ATP binding site of EGFR tyrosine kinase in a similar pose as that of the standard drug gefitinib. CONCLUSION: The potential anticancer activity of compounds 6h and 6j was confirmed and need further exploration in cancer cell lines of different tissue origin and signaling pathways, as well as in animal models of cancer development.

Recent advancement in the discovery and development of anti-epileptic biomolecules: An insight into structure activity relationship and Docking.

Although there have been many advancements in scientific research and development, the cause of epilepsy still remains an open challenge. In spite of high throughput research in the field of anti-epileptic drugs, efficacy void is still prevalent before the researchers. Researchers have persistently been exploring all the possibilities to curb undesirable side effects of the anti-epileptic drugs or looking for a more substantial approach to diminish or cure epilepsy. The drug development has shown a hope to medicinal chemists and researchers to carry further research by going through a substantial literature survey. This review article attempts to describe the recent developments in the anti-epileptic agents, pertaining to different molecular scaffolds considering their structure-activity relationship, docking studies and their mechanism of actions.

Lipid-based nanoformulations in the treatment of neurological disorders.

The neurological disorders affect millions of people worldwide, and are bracketed as the foremost basis of disability-adjusted life years (DALYs). The treatment options are symptomatic and often the movement of drugs is restricted by a specialized network of endothelial cell layers (adjoined by tight cell-to-cell junction proteins; occludin, claudins, and junctional adhesion molecules), pericytes and astroglial foot processes. In recent years, advances in nanomedicine have led to therapies that target central nervous system (CNS) pathobiology via altering signaling mechanisms such as activation of PI3K/Akt pathway in ischemic stroke arrests apoptosis, interruption of α-synuclein aggregation prevents neuronal degeneration in Parkinson's. Often such interactions are limited by insufficient concentrations of drugs reaching neuronal tissues and/or insufficient residence time of drug/s with the receptor. Hence, lipid nanoformulations, SLNs (solid lipid nanoparticles) and NLCs (nanostructured lipid carriers) emerged to overcome these challenges by utilizing physiological transport mechanisms across blood-brain barrier, such as drug-loaded SLN/NLCs adsorb apolipoproteins from the systemic circulation and are taken up by endothelial cells via low-density lipoprotein (LDL)-receptor mediated endocytosis and subsequently unload drugs at target site (neuronal tissue), which imparts selectivity, target ability, and reduction in toxicity. This paper reviews the utilization of SLN/NLCs as carriers for targeted delivery of novel CNS drugs to improve the clinical course of neurological disorders, placing some additional discussion on the metabolism of lipid-based formulations.

3'-(4-(Benzyloxy)phenyl)-1'-phenyl-5-(heteroaryl/aryl)-3,4-dihydro-1'H,2H-[3,4'-bipyrazole]-2-carboxamides as EGFR kinase inhibitors: Synthesis, anticancer evaluation, and molecular docking studies.

Pyrazoline-linked carboxamide derivatives were designed, synthesized, and evaluated for potential epidermal growth factor receptor (EGFR) kinase inhibition, anticancer activity, and apoptotic and cardiomyopathy toxicity. Compounds 6m and 6n inhibit EGFR kinase at a concentration of 6.5 ± 2.91 and 3.65 ± 0.54 µM, respectively. Some of these compounds showed effects on proliferation, which were also then evaluated against four different human cancer cell lines, that is, MCF-7 (breast cancer), A549 (non-small-cell lung tumor), HCT-116 (colon cancer), and SiHa cells (cancerous tissues of the cervix uteri). The results showed that certain synthetic compounds showed significant inhibitor activity; compounds 6m and 6n were more cytotoxic than doxorubicin against A549 cancer cells, with IC50 values of 10.3 ± 1.07 and 4.6 ± 0.57 µM, respectively. Additionally, compounds 6m and 6n induced apoptosis in A549 cancer cells, as evidenced by 4',6-diamidino-2-phenylindole (DAPI) staining and phase-contrast microscopy. Potency to induce apoptosis by compound 6n was further confirmed by fluorescence-activated cell sorting using Annexin V-FITC and propidium iodide labeling. Compound 6n showed normal cardiomyocytes with no marked sign of pyknotic nuclei in cardiomyopathy and also normal histological appearance of the renal cortex when compared with that of control. Results of molecular docking studies suggested that compounds 6m and 6n can bind to the hinge region of the adenosine triphosphate-binding site of EGFR kinase, like the standard drug erlotinib. Therefore, the present study suggests that compounds 6m and 6n have potent in vitro antitumor activities against the human non-small-cell lung tumor cell line A549, which can be further explored in other cancer cell lines and in animal studies.

Antimicrobial properties of starch films incorporated with chitosan nanoparticles: In vitro and in vivo evaluation.

Chitosan nanoparticles (CNP) were synthesized via ionic gelation and used for the preparation of starch-based nanocomposite films containing different concentration of CNP (0, 5, 10, 15, 20% w/w). Antimicrobial properties of starch/CNP films was evaluated via in vitro (disc diffusion analysis) and in vivo (microbial count in wrapped cherry tomatoes) study. It was found that inhibitory zone of the 15 and 20% of starch/CNP films were clearly observed for all the tested bacteria including Bacillus cereus, Staphylococcus aureus, Escherichia coli and Salmonella typhimurium. In vivo study revealed that the starch/CNP film (15% w/w) was more efficient to inhibit the microbial growth in cherry tomatoes (7 × 102 CFU/g) compared to neat starch film (2.15 × 103 CFU/g) thus confirmed the potential application of the films as antimicrobial food packaging.

Embozene Loaded Prostatic Artery Embolization

@#Herein is a case report of a 70 years old man with a tenacious benign prostatic hyperplasia (BPH). The aim of this manuscript is to briefly discuss the usage and advantage of EmbozeneTM Microsphere in embolization of the prostate arteries in the treatment of failed medical and surgical therapy for BPH.