3CL like protease (3CLpro or Mpro) is one of the main proteases of 2019-nCoV. The 3CLpro is a nonstructural protein of SARS-CoV and has an essential role in viral replication and transcription, thus, could be a potential target for anti-SARS drug development. The present study employed ligand-and structure-based approaches to identify the potent inhibitors of 2019-nCoV protease. The e-pharmacophore developed from 3CLpro-1 yielded virtual hits, that were subjected through drug likeliness and PAINS filters to remove interfering compounds. Further comprehensive docking studies, free energy calculations and ADMET studies resulted in two virtual leads-MolPort-000-410-348 and MolPort-002-530-156. The compounds MolPort-000-410-348 and MolPort-002-530-156 displayed good docking score of À12.09 and À13.38 Kcal/mol and free binding energy of À63.34 ± 2.03 and À61.52 ± 2.24 Kcal/ mol, respectively. The compounds also exhibited satisfactory predicted ADMET profile and were subjected to molecular dynamic (MD) studies. The MD simulation produced stable complexes of these ligands with 3CLpro protein and ligand RMSD in acceptable limits.

Gloriosine, a colchicine-like natural product, is widely obtained from Gloriosa superba roots. Despite having remarkable anticancer potential, colchicine could not pave its way to the clinic, while gloriosine is yet to be investigated for its pharmacological effects. In the present work, 14 compounds, including gloriosine, were isolated from the G. superba roots and were characterized by NMR spectroscopy. Gloriosine ( 11 ) was evaluated for its antiproliferative activity against a panel of 15 human cancer cell lines of different tissues and normal breast cells. Gloroisine ( 11 ) displayed significant antiproliferative activity against various cancer cell lines selectively, with IC 50 values ranging from 32.61 to 100.28 nM. Further, gloriosine ( 11 ) was investigated for its apoptosis-inducing ability and found to form apoptotic bodies. It also inhibited A549 cell migration in the wound healing assay. Finally, molecular docking studies were performed to explore the possible binding modes of gloriosine with the colchicine-binding site of tubulin protein. Our findings suggested that gloriosine might be a potential lead for anticancer drug discovery.

Here we report a facile method for the synthesis of nickel oxide-nickel (NiO@Ni) Mott-Schottky catalyst employing metalorganic framework (MOF) as the precursor. A direct amidation protocol of aldehydes with amines has been optimized under mild conditions using NiO@Ni Mott-Schottky catalyst and it shows far better catalytic activity than the NiOÀ Ni nanoparticles prepared from simple Ni 2 + salt under similar reaction conditions. The heterogeneous catalyst is robust, recyclable and efficient to provide comparable yield to costly ligand-based homogeneous Ni catalysts. The scope of the reaction protocol has been explored with variably substituted substrates. The reaction initiates by homolytic cleavage of peroxide and proceeds through radical mechanism.

: Cyclin-dependent kinases (CDKs) is a group of multifunctional enzymes consisting of catalytic and regulatory subunits. The regulatory subunit, cyclin remain dissociated under normal circumstances, complexation of cyclin with the catalytic subunit of CDK leads to its activation for phosphorylation of protein substrates. The primary role of CDKs is in the regulation of the cell cycle. Retinoblastoma protein (Rb) is one of the widely investigated tumor suppressor protein substrate of CDK, which prevent cells from entering into cell-cycle under normal conditions. Phosphorylation of Rb by CDKs causes its inactivation and ultimately allows cells to enter a new cell cycle. Many cancers are associated with hyperactivation of CDKs as a result of mutation of the CDK genes or CDK inhibitor genes. Therefore, CDK modulators are of great interest to explore as novel therapeutic agents against cancer and led to the discovery of several CDK inhibitors to clinics. This review focuses on the current progress and development of anti-cancer CDK inhibitors from preclinical to clinical and synthetic to natural small molecules.

Ipomone (1), a novel diterpenoid along with seven known compounds (2–8), was isolated for the first time from the acidified hydroalcoholic extract of Ipomoea nil seeds. The structures of the isolated compounds were elucidated via comprehensive NMR spectroscopic data. The absolute configuration of 1 was ascertained through NOESY, NMR, and ECD analyses. Compound 1 was found to contain an unusual bicyclo-[3.2.1] octanone, which appeared first time in any natural product that might be an artifact resulting from the acid-catalyzed 1,2 alkyl shift/rearrangement. The novel compound was screened for cytotoxic activity against a panel of 12 human cancer cell lines and exhibited weak cytotoxicity with IC50 values in the range of 34–86 μM (except for HEK-293 cells). Microscopic studies revealed that compound 1 induced apoptosis and autophagy in A549 cells. To further explore the signaling pathway involved, immunoblot analysis was performed that confirmed inhibition of apoptotic proteins PARP-1 and caspase-3 expression and upregulation of LC3B expression by compound 1. The compound was further subjected to molecular docking studies to evaluate its binding affinity with p110α, PARP-1, and caspase-3 proteins.

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A HP20 resin-based unique method was adopted to get an active fraction of the hydroalcoholic extract of G. glabra roots. The fraction showed potent cytotoxicity against cancer cell line and was further subjected to detailed phytochemical investigation to obtain ten biomarkers. The isolated compounds were also tested for the cytotoxicity against the C6 Glioma cell line in vitro using MTT assay. Among the isolated compounds, glycyrrhetic acid (1), glabrol (6), and glabridin (9) exhibited significant cytotoxicity. The compounds showed a dose-dependent decrease in cell viability. The active compounds were subjected to molecular docking study against topoisomerase I and topoisomerase II to support the mechanism of antitumor activity.

The Spike (S) protein of SARS-CoV-2 expressed on the viral cell surface is of particular importance as it facilitates viral entry into the host cells. The S protein is heavily glycosylated with 22 N-glycosylation sites and a few N-glycosylation sites. During the viral surface protein synthesis via the host ribosomal machinery, glycosylation is an essential step in post-translational modifications (PTMs) and consequently vital for its life cycle, structure, immune evasion, and cell infection. Interestingly, the S protein of SARS-CoV-2 and the host receptor protein, ACE2, are also extensively glycosylated and these surface glycans are critical for the viral–host cell interaction for viral entry. The glycosylation pathway of both virus (hijacked from the host biosynthetic machinery) and target cells crucially affect SARS-CoV-2 infection at different levels. For example, the glycosaminoglycans (GAGs) of host cells serve as a cofactor as they interact with the receptor-binding domain (RBD) of S-glycoprotein and play a protective role in host immune evasion via masking the viral peptide epitopes. Hence, the post-translational glycan biosynthesis, processing, and transport events could be potential targets for developing therapeutic drugs and vaccines. Especially, inhibition of the N-glycan biosynthesis pathway amplifies S protein proteolysis and, thus, blocks viral entry. The chemical inhibitors of SARS-CoV-2 glycosylation could be evaluated for Covid-19. In this review, we discuss the current status of the chemical inhibitors (both natural and synthetically designed inhibitors) of viral glycosylation for Covid-19 and provide a future perspective. It could be an important strategy in targeting the various emerging SARS-CoV-2 variants of concern (VOCs), as these inhibitors are postulated to aid in reducing the viral load as well as infectivity.