EGFR, HER2 target based molecular docking analysis, in vitro screening of 2, 4, 5-trisubstituted imidazole derivatives as potential anti-oxidant and cytotoxic agents.

In our endeavor towards the development of potent molecules for cancer diseases, we have designed and synthesized a series of 2,4,5-trisubstituted imidazole derivatives (B1-B24) and characterized by using various spectroscopic techniques. All these compounds are further evaluated for their in vitro anti-cancer, anti-oxidant activities and molecular docking studies against EGFR, HER2 protein receptors. The in vitro anti-cancer activity analysis reveals that compounds B11 and B16 were found to be effective scaffolds against the tested human cancer cell lines IMR-32, A549 and HeLa. Particularly, B16 and B11 showed effective cytotoxicity against A549 and IMR-32 with IC50 values of 09.521±0.54µM and 10.294±0.43µM, respectively. Moreover, compounds B17, B18 and B23 showed potent activity towards the anti-oxidant screening with IC50 values of 5.87±1.73µM, 6.29±1.27µM and 4.95±1.81µM, respectively compared to standard ascorbic acid. Molecular docking was performed against the EGFR, HER2 protein receptors to provide more insight into their mechanism of interaction by comparing with standard EGFR, HER2 inhibitors like Gefitinib (EFGR), Lapatanib (EGFR), Afitinib (HER2) and Canertinib (HER2). Compounds B15, B16, B11 and B10 were exhibiting their minimum binding energies. Out of the aforementioned docked molecules, B15 and B16 showed the best binding energies of -11.15kcalmol-1, -10.70kcalmol-1 and -10.49kcalmol-1, -10.12kcalmol-1 against EGFR and HER2 protein receptors, respectively. The molecular docking results are well corroborated with the in vitro anti-cancer activity finding.

Design, synthesis and biological evaluation of 8-substituted-6-hydrazonoindolo[2,1-b]quinazolin-12(6H)-one scaffolds as potential cytotoxic agents: IDO-1 targeting molecular docking studies.

Herein, we have reported the synthesis of 18 novel 8-substituted tryptanthrin analogues based on our earlier work. All these tryptanthrin analogues were well characterized by 1H &13C NMR, FT-IR, Mass Spectrometry and Elemental Analysis. All these 8-substituted analogues were screened for their anti-oxidant activity by DPPH radical scavenging assay. Out of all the tested compounds, T11, T12, T17 and T18 showed potent anti-oxidant activity. The anti-cancer activity have been performed by using MTT assay protocol and their results depicts that compounds having the 4-pyridyl or 4-carboxyphenyl substituents at the 8th position of the tryptanthrin framework are found to be the most promising cytotoxic agent against A549, MCF-7 and HeLa human cancer cell lines compared to others as well as with the standard drug cisplatin. Moreover, the comparative molecular docking studies against the three protein receptors IDO1, EGFR and HER2 strongly suggested that IDO1 is the best target protein, which exhibits lowest binding energies of -11.73 and -11.61kcalmol-1 for T11 and T12 scaffolds, respectively towards the in vitro anti-cancer activity.