Showing papers by "Mohane Selvaraj Coumar published in 2020"
TL;DR: A novel role of BIRC5 is revealed in cancer cells as a direct regulator of autophagy, which regulates the interplay between mitosis, apoptosis, andAutophagy in embryonic and cancer cells.
Abstract: BIRC5/Survivin is known as a dual cellular functions protein that directly regulates both apoptosis and mitosis in embryonic cells during embryogenesis and in cancer cells during tumorigenesis and ...
77 citations
TL;DR: The novel quinoline CSV0C018875 could be further optimized to improve the ADME as well pharmacodynamic property and binds deeper inside the active site cavity of G9a, which facilitates the tight binding and also increases the compounds residence time, which reflects better G 9a inhibition.
12 citations
TL;DR: LCL161 has the potential for use in the management of cancer patients with ABCB1 and BIRC5-related drug resistance and the findings of this study provide important information to physicians for designing a more "patient-specific" LCL161 clinical trial program in the future.
8 citations
TL;DR: Structural modification at the 6- and 7-position of quinazoline core of 1 led to the identification of 34 as an orally bioavailable multi-kinase inhibitor, which exhibits potent anti-proliferative activity against various cancer cell lines.
6 citations
TL;DR: The drug-like natural product analog 6a constitutes a highly promising new anticancer lead, which has >3-fold higher antiproliferative activity than fasudil in SW480 cells and inhibits the migration of colon cancer cells and induces cell apoptosis.
Abstract: Among the plant constituents of Clerodendrum colebrookianum Walp., acteoside, martinoside, and osmanthuside β6 interact with ROCK, a drug target for cancer. In this study, aglycone fragments of the...
5 citations
TL;DR: Promising in silico outcomes suggest that the designed compounds could be suitable anti-cancer leads that need to be synthesized and tested in various cancer cell lines.
Abstract: Rho-associated coiled-coil protein kinase (ROCK) is playing a vital role in the regulation of key cellular events and also responsible for causing several pathological conditions such as cancer, hypertension, Alzheimer's, cerebral vasospasm, and cardiac stroke. Therefore, it has attracted us to target ROCK protein as a potential therapeutic target for combating various diseases. Consequently, we investigated the active site of ROCK I protein and designed novel leads against the target using the de novo evolution drug design approach. Caffeic acid (an aglycone of acteoside) as a scaffold and fragments from 336 reported ROCK inhibitors were used for the design of novel leads. Multiple copy simultaneous search docking was used to identify the suitable fragments to be linked with the scaffold. Basic medicinal chemistry rules, coupled with structural insights generated by docking, led to the design of 7a, 8a, 9a, and 10a as potential ROCK I inhibitors. The designed leads showed better binding than the approved drug fasudil and also interacted with the key hinge region residue Met156 of ROCK I. Further, molecular dynamics (MD) simulation revealed that the protein-ligand complexes were stable and maintained the hydrogen bond with Met156 throughout the MD run. The promising in silico outcomes suggest that the designed compounds could be suitable anti-cancer leads that need to be synthesized and tested in various cancer cell lines. Graphical abstract.
2 citations
TL;DR: The results showed that MOBifi could design novel molecules that could be further tested in the laboratory for diabetes treatment and could be extended for other multi-objective optimization problems as well.
2 citations