Hepatoprotective effect of flavonoid rich fraction of Sesbania grandiflora: Results of In vivo, in vitro, and molecular docking studies.

Background: Phytochemicals and their derivatives are promising target drugs for various ailments and have served as therapeutic agents for several decades. Using in vivo and in vitro models and molecular docking, this study investigated the pharmacological potential of a flavonoid-rich fraction of the ethanolic extract of Sesbania grandiflora (SG).

Objectives: This research aimed to determine whether flavonoid-rich whole-plant extracts of SGs have any cytoprotective or in vivo hepatoprotective effects.

Strategies in the Design and Development of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs).

AIDS (acquired immunodeficiency syndrome) is a potentially life-threatening infectious disease caused by human immunodeficiency virus (HIV). To date, thousands of people have lost their lives annually due to HIV infection, and it continues to be a big public health issue globally. Since the discovery of the first drug, Zidovudine (AZT), a nucleoside reverse transcriptase inhibitor (NRTI), to date, 30 drugs have been approved by the FDA, primarily targeting reverse transcriptase, integrase, and/or protease enzymes.

Repurposing drugs targeting epidemic viruses.

For emerging and re-emerging epidemic infections, researchers face challenges to develop broad-spectrum antivirals as well as reducing development time and costs, and drug resistance. Drug repurposing is a reliable strategy for rapidly discovering potent new antiviral agents, reducing the need for clinical trials. In this review, we outline antiviral drug candidates identified using the drug repurposing approach, with their potential modes of action and biological responses against various epidemic viral infectious diseases.

Hydroxytriazenes incorporating sulphonamide derivatives: evaluation of antidiabetic, antioxidant, anti-inflammatory activities, and computational study.

The existent investigation deals with synthesis, characterization, computational analysis, and biological activities of some hydroxytriazene derivatives containing sulphonamide moiety. The compounds were screened for antidiabetic, antioxidant, and anti-inflammatory activities. The antidiabetic activity was assessed using α-glucosidase and α-amylase inhibition assays with IC values ranging from 32.

Novel naphthyl based 1,2,4-trioxanes: Synthesis and in vivo efficacy in the Plasmodium yoelii nigeriensis in Swiss mice.

A new series of 1,2,4-trioxanes 9a1-a4, 9b1-b4, 10-13 and 9c1-c4 were synthesized and evaluated against multidrug-resistant Plasmodium yoelii nigeriensis in Swiss mice via oral and intramuscular (i.m.) routes.

Structural Insights to Human Immunodeficiency Virus (HIV-1) Targets and Their Inhibition.

Human immunodeficiency virus (HIV) is a deadly virus that attacks the body's immune system, subsequently leading to AIDS (acquired immunodeficiency syndrome) and ultimately death. Currently, there is no vaccine or effective cure for this infection; however, antiretrovirals that act at various phases of the virus life cycle have been useful to control the viral load in patients. One of the major problems with antiretroviral therapies involves drug resistance.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs): a brief overview of clinically approved drugs and combination regimens.

The non-nucleoside reverse transcriptase inhibitors (NNRTIs) are allosteric inhibitors of HIV-1 reverse transcriptase and are classified into generations depending on their discovery and resistance profiles. The NNRTIs are used in combination regimens with antiretroviral agents that target two or more enzymes in the viral life cycle. The combination regimens usually include a backbone of two nucleoside or nucleotide reverse transcriptase inhibitors and a third core agent among the NNRTIs or protease inhibitors.

Synthesis, antidiabetic, antioxidant and anti-inflammatory activities of novel hydroxytriazenes based on sulpha drugs.

The present study is aimed to investigate the anti-inflammatory, antioxidant and antidiabetic activities of three series of hydroxytriazenes based on sulfa drugs viz; Sulphathiazole (ST), Sulfisoxazole (SF) and Sulphamethoxazole (SM). Antidiabetic activities of the synthesized hydroxytriazenes were investigated by α-glucosidase and α-amylase inhibition method and IC values were recorded. The compounds presented significant α-glucosidase and α-amylase inhibition effect with IC values ranging from 122 to 341 μg/mL.

Synthesis of sulpha drug based hydroxytriazene derivatives: Anti-diabetic, antioxidant, anti-inflammatory activity and their molecular docking studies.

Herein, we report synthesis, characterization, anti-diabetic, anti-inflammatory and anti-oxidant activities of hydroxytriazenes derived from sulpha drugs, namely sulphanilamide, sulphadiazine, sulphapyridine and sulphamethazine. Before biological screening of the compounds, theoretical prediction using PASS was done which indicates probable activities ranging from Pa (probable activity) values 65-98% for anti-inflammatory activity. As per the predication, experimental validation of some of the predicted activities particularly anti-diabetic, anti-inflammatory and anti-oxidant was done.

Catalyst- and Solvent-Free Coupling of 2-Methyl Quinazolinones and Isatins: An Environmentally Benign Access of Diastereoselective Schizocommunin Analogues.

An environmentally benign highly atom-economic protocol for the construction of the C-C bond has been developed under catalyst- and solvent-free conditions. This protocol involves the efficient coupling of 2-methyl quinazolinones with isatin for the highly diastereoselective access of schizocommunin derivatives in excellent yields (up to 97%). Furthermore, the preliminary cytotoxicity screening of selected schizocommunin analogues displayed promising anticancer activity against human cancer cell lines, and the cytotoxic potential of active compound was also validated by in silico molecular docking simulation studies.

The Journey of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from Lab to Clinic.

Human immunodeficiency virus (HIV) infection is now pandemic. Targeting HIV-1 reverse transcriptase (HIV-1 RT) has been considered as one of the most successful targets for the development of anti-HIV treatment. Among the HIV-1 RT inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have gained a definitive place due to their unique antiviral potency, high specificity, and low toxicity in antiretroviral combination therapies used to treat HIV.

HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: SAR and Lead Optimization Using CoMFA and CoMSIA Studies (1995-2016).

Background: Design of inhibitors for HIV-1 reverse transcriptase inhibition (HIV-1 RT) is one of the successful chemotherapies for the treatment of HIV infection. Among the inhibitors available for HIV-1 RT, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have shown to be very promising and clinically approved drugs. However, the efficiency of many of these drugs has been reduced by the drug-resistant variants of HIV-1 RT.

Evaluation of 4-thiazolidinone derivatives as potential reverse transcriptase inhibitors against HIV-1 drug resistant strains.

Rapid emergence of drug resistance is crucial in management of HIV infection limiting implementation of efficacious drugs in the ART regimen. Designing new molecules against HIV drug resistant strains is utmost essential. Based on the anti-HIV-1 activity, we selected four 4-thiazolidinone derivatives (S009-1908, S009-1909, S009-1911, S009-1912) and studied their interaction with reverse transcriptase (RT) from a panel of 10 clinical isolates (8 nevirapine resistant and two susceptible) using in silico methods, and inhibition pattern using in vitro cell based assays.

Rational design and synthesis of novel thiazolidin-4-ones as non-nucleoside HIV-1 reverse transcriptase inhibitors.

A series of novel thiazolidin-4-one analogues, characterized by different substitution patterns at positions C-2 and N-3 of the thiazolidin-4-one scaffold for anti-HIV-1 activity has been investigated. Most of the compounds showed anti-HIV-1 activity at micromolar concentrations when tested in TZM-bl cells in vitro. Among the thirty-three compounds tested, compound 16 was the most potent inhibitor of HIV-1 replication against HIV-1IIIB, HIV-1ADA5, HIV-1UG070 and HIV-1VB59 (EC50=0.

Lead optimization at C-2 and N-3 positions of thiazolidin-4-ones as HIV-1 non-nucleoside reverse transcriptase inhibitors.

Based on rational drug design approach, a series of novel thiazolidin-4-ones bearing different aryl/heteroaryl moieties at position C-2 and N-3 are synthesized and evaluated as potent inhibitors for human immunodeficiency virus type-1 reverse transcriptase enzyme (HIV-1 RT). An in vitro HIV-1 RT assay showed that the compounds 4, 5, 6, 8, 12, 13, 14 and 17 have shown high inhibition of reverse transcriptase (75.41, 95.

CoMFA and CoMSIA of diverse pyrrolidine analogues as dipeptidyl peptidase IV inhibitors: active site requirements.

The inhibition of dipeptidyl peptidase IV (DPP-IV) has emerged as an attractive target in the treatment of type 2 diabetes. In view of this development, a critical analysis of structural requirements of the DPP-IV inhibitors is envisioned to identify the significant features toward design of selective inhibitors. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) contour plots of pyrrolidine based analogues are used to analyze the structural requirements of a DPP-IV active site.

CoMFA and CoMSIA studies on thiazolidin-4-one as anti-HIV-1 agents.

Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on thiazolidin-4-one class of compounds as HIV-1 reverse transcriptase (HIV-1 RT) inhibitors using global minima and crystal structure conformations. Results obtained from the crystal structure-based model yielded superior statistical data (r(cv)(2) values of 0.683 for CoMFA and 0.