Design, synthesis and biological evaluation of new series of hexahydroquinoline and fused quinoline derivatives as potent inhibitors of wild-type EGFR and mutant EGFR (L858R and T790M) was written by Shaheen, Mennatallah A.;El-Emam, Ali A.;El-Gohary, Nadia S.. And the article was included in Bioorganic Chemistry in 2020.Product Details of 55490-87-4 This article mentions the following:
New series of hexahydroquinoline and fused quinoline derivatives were designed and synthesized. The thirty seven new compounds were screened for in vitro antitumor activity against HepG2, HCT-116 and MCF-7 cancer cells. Results indicated that certain compounds, including I, have the strongest potency against the three cancer cells, and they were further screened for in vitro cytotoxicity against A431 and H1975 cancer cells, as well as WI38 and WISH normal cells. Results revealed that I potently inhibited the growth of H1975 cells harboring EGFRT790M mutation (IC50 = 1.32 ± 0.2μM) over A431 cells overexpressing EGFRWT (IC50 = 4.96 ± 0.3μM). Moreover, the seven compounds displayed low cytotoxicity against the tested normal cells. The seven potent antitumor compounds were examined for their ability to inhibit the activity of EGFRWT. The attained data manifested that I has remarkable EGFRWT inhibitory activity (IC50 = 0.083 ± 0.002μM) compared to erlotinib (IC50 = 0.067 ± 0.002μM). Compound I was further studied for its enzymic inhibitory activity against other eight human kinases, and it displayed outstanding inhibitory activity against EGFRL858R and EGFRT790M mutants (IC50 = 0.053 ± 0.002, 0.026 ± 0.001μM, resp.), as well as JAK3 (IC50 = 0.069 ± 0.003μM). Anal. of cell cycle evidenced that I induces cell cycle arrest in G2/M and pre-G1 phases in the tested cancer cells. In addition, cancer cell death induced by I was proved to take place via apoptosis supported by elevated Bax/Bcl-2 ratio in the tested cancer cells. Moreover, docking results confirmed the good binding interactions of I with EGFRWT, EGFRL858R, EGFRT790M and JAK3, which came in agreement with the results of in vitro enzyme assay. Further, I is predicted to have good oral absorption, good drug-likeness properties and low toxicity risks in human. In the experiment, the researchers used many compounds, for example, 2-(Anthracen-9-ylmethylene)malononitrile (cas: 55490-87-4Product Details of 55490-87-4).
2-(Anthracen-9-ylmethylene)malononitrile (cas: 55490-87-4) belongs to nitriles. The R-C-N bond angle in and nitrile is 180° which give a nitrile functional group a linear shape. Both the carbon and the nitrogen are sp hydridized which leaves them both with two p orbitals which overlap to form the two π bond in the triple bond. Asymmetric bioreduction of nitriles is an attractive route to produce optically active nitriles as current metal-catalyzed hydrogenations tend to have low reactivity.Product Details of 55490-87-4
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts