The activity prediction of indole inhibitors against HCV NS5B polymerase

Abstract

Non-structural viral protein 5B (NS5B) is a viral protein in hepatitis C virus.Although various inhibitors against NS5B have been found, the activity prediction of similar untested inhibitors is still highly desirable. In this respect, the Tchebichef moments (TMs) calculated from the images of molecular structures were regarded as the independent variables while the inhibitory activity (pIC 50 ) was the dependent variable, and the predictive model was established by means of stepwise regression. The R-squared of leave-one-out cross-validation (Q 2 ) for the training set and the R-squared of prediction (R 2 p ) for external independent test set were 0.919 and 0.927, respectively. The obtained model was also evaluated strictly. Compared with the multivariate curve resolution with alternating least squares (MCR-ALS) and the QSAR approaches derived from the literature, the proposed method is more accurate and reliable. This study not only provides an effective approach to predict the biological activity of RNA replication's inhibitors, but also extends the QSAR modeling technique. K E Y W O R D Sbiological activity prediction model, hepatitis C virus, NS5B polymerase inhibitors, quantitative structure-activity relationship, Tchebichef image moments

The antimalarial activity of indole alkaloids and hybrids

“…Indole derivatives have the ability to act on various enzymes and receptors, inclusive of efflux pump, topoisomerase, transcriptase, integrase, protease, pyruvate kinase, histone deacetylase, histone acetyltransferases, proviral insertion site in Moloney murine leukemia virus, filamentous temperature-sensitive protein Z, and tubulin. [6] Accordingly, indole derivatives possess diverse biological and pharmacological properties such as antibacterial, [7,8] anticancer, [9,10] antifungal, [11,12] antileishmanial, [13,14] antihepatitis virus C (HCV), [15,16] anti-HIV, [17,18] antitubercular, [19,20] and antimalarial [21,22] activities. Many indole derivatives such as osimertinib, panobinostat lactate, and anlotinib dihydrochloride ( Figure 1) have already been used in clinics for the treatment of various diseases, revealing that indole derivatives play a critical role for the discovery of new drugs.…”

Discovery of Novel HCV NS5B polymerase inhibitor, 2‐(3,4‐dimethyl‐5,5‐dioxidobenzo[e]pyrazolo[4,3‐c][1,2]thiazin‐2(4H)‐yl)‐N‐(2‐fluorobenzyl)acetamide via molecular docking and experimental approach

“…12,13 The synthetic compounds from various reports have been potent inhibitors of HCV NS5B polymerase. [14][15][16][17] The compounds from pyrazolobenzothiazine have gained significance as antiviral inhibitors. For instance, many of its derivatives have been explored as anti-human immunodeficiency virus (HIV) agents.…”