Synthesis and anticancer activity of new isatin-benzoic acid conjugates

Abstract

A series of new isatin-benzoic acid conjugates (9a - n) were synthesized via conjugation of isatin (3a) and its derivatives (3b - d, 4, 5 and 6) with 4-amino-5 chloro-2-ethoxybenzoic acid or 4-amino-5-(ethylsulfonyl)-2- methoxybenzoic acid by using chloroacetyl chloride as a bifunctional linker. Compounds 3a - d were prepared by employing Sandmeyer reaction. Compounds 4, 5, and 6 were obtained from isatin (3a) via previously reported methods. Isatin-benzoic acid conjugates were synthesized by halomethylketo alkylation at N-1 position of the isatin nucleus. The newly synthesized compounds were characterized using IR, Mass, ¹H NMR and ¹³C NMR spectral techniques. Anticancer activity of the synthesized compounds was evaluated againstMCF-7 (human breast cancer) and HeLa (human cervical cancer) cell lines by 3-(4,5-dimethylthiazol -2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay using vinblastin as a standard. The results showed compounds 9g and 9d to be more potent than the other compounds synthesized with IC₅₀ values of 5.88 ± 0.88 & 6.57 ± 0.81 μM against MCF-7, and 8.34 ± 0.94 & 9.24 ± 1.06 μM against HeLa, respectively.

Keywords: synthesis, isatin-benzoic acid conjugates, in vitro anticancer, human breast cancer cell line, human cervical cancer cell line