Synthesis and Anti-Proliferative Activity of Biphenyl Derived 5-Substituted-Indolin-2-Ones

Abstract

A series of novel biphenyl derived 5-substituted-indolin-2-one derivatives were synthesized by the reaction of 6-chloro-5-(2-chloroethyl)-indolin-2-one 1 with cyclic secondary amines 2a-h followed by condensation of bromomethylcyanobiphenyl to afford the compounds 5a-h. The nitrile group of 5a-h was converted into tetrazole to obtain the compounds 7a-h and tetrazole of 7a-h was further ring transformed into oxadiazole to get compounds 8a-h. Molecular docking study of these previously unknown molecules was performed on PDB: 453D to analyze the interaction and preferred binding mode of synthesized molecules with DNA. Anti-proliferative activity of these newly synthesized compounds were evaluated against a panel of 60 human cancer cell lines at National Cancer Institute (NCI), Bethesda USA. Among these, seven (07) compounds were evaluated for their anticancer activity. Some of the compounds displayed potent anti-proliferative activity at 10 µM.

Synthesis and Cytotoxic Activity of Chiral Sulfonamides Based on the 2-Azabicycloalkane Skeleton

“…In addition to functional groups, certain characteristic structural motifs are also associated with impressive biological activity. For example, the biphenyl moiety is present in numerous derivatives that have been tested in antiproliferative studies [6][7][8]. The trifluoromethyl group is also regarded as a valuable pharmacophore [9], which is found in marketed drugs (e.g., nonsteroidal antiandrogen flutamide) and newly developed derivatives [10].…”

“…We used these amines and their epimers for the construction of bifunctional catalysts [22]. Monomeric and dimeric derivatives modified with amino functions were also prepared and were found to inhibit the growth of selected tumor cell lines [7].…”

“…We used these amines and their epimers for the construction of bifunctional catalysts [22]. Monomeric and dimeric derivatives modified with amino functions were also prepared and were found to inhibit the growth of selected tumor cell lines [7]. The promising results of our study on the biological activity of amines bearing chiral azabicyclic skeletons prompted us to prepare a series of corresponding sulfonamides.…”