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Discovering a potential drug for HCV treatment is a challenging task in the field of drug research. This study initiates with computational screening and modeling of promising ligand molecules. The foremost modeling method involves the identification of novel compound and its molecular interaction based on pharmacophore features. A total of 197 HCV compounds for NS3/4A protein target were screened for our study. The pharmacophore models were generated using PHASE module implemented in Schrodinger suite. The pharmacophore features include one hydrogen bond acceptor, one hydrogen bond donor, and three hydrophobic sites. As a result, based on mentioned hypothesis the model ADHHH.159 corresponds to the CID 59533233. Furthermore, docking was performed using maestro for all the 197 compounds. Among these, the CID 59533313 and 59533233 possess the best binding energy of −11.75 and − 10.40 kcal/mol, respectively. The interactions studies indicated that the CID complexed with the NS3/4A protein possess better binding affinity with the other compounds. Further the compounds were subjected to calculate the ADME properties. Therefore, it can be concluded that these two compounds could be a potential alternative drug for the development of HCV.

Claudin‐4 (CLDN4) is a vital member of tight‐junction proteins that is often overexpressed in cancer and other malignancies. The three‐dimensional structure of human CLDN4 was constructed based on homology modeling approach. A total of 265 242 molecules from the National Cancer Institute (NCI) database has been utilized as a dataset for this study. In the present work, structure‐based virtual screening is performed with the NCI database using Glide. By molecular docking, 10 candidate molecules with high scoring functions, which binds to the active site of CLDN4 were identified. Subsequently, molecular dynamics simulations of membrane protein were used for optimization of the top‐three lead compounds (NCI110039, NCI344682, and NCI661251) with CLDN4 in a dynamic system. The lead molecule from NCI database NCI11039 (purpurogallin carboxylic acid) was synthesized and cytotoxic properties were evaluated with A549, MCF7 cell lines. Our docking and dynamics simulations predicted that ARG31, ASN142, ASP146, and ARG158 as critically important residues involved in the CLDN4 activity. Finally, three lead candidates from the NCI database were identified as potent CLDN4 inhibitors. Cytotoxicity assays had proved that purpurogallin carboxylic acid had an inhibitory effect towards breast (MCF7) and lung (A549) cancer cell lines. Computational insights and in vitro (cytotoxicity) studies reported in this study are expected to be helpful for the development of novel anticancer agents.

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A series of novel quinoline appended biaryls have been synthesized (5a−5o) by reacting various substituted boronic acids (4e−4h) with various substituted 2-(4-bromophenoxy)quinolin-3-carbaldehydes (3a−3d) through carbon−carbon bond formation. Effects of various quinoline appended biaryls (5a−5o) on the breast cancer protein 3ERT are moderate to high, as found by in silico molecular docking studies. Comparatively, all quinoline appended biaryls (5a−5o) 5h show better efficacy with a binding energy of −9.39 kcal/mol, and hydrogen bonds are Thr347, Glu353, and Arg394 in the binding pocket. Conclusively, the final novel quinoline appended biaryls (5a−5o) have been confirmed with all the spectral studies, and their efficacy has been validated with in silico studies.

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