In Vitro Bioactivities of Isoindolin-1-3-Phosophonate Compounds

Abstract

In this work an efficient synthesis of isoindolin-1-one-3-phosphonates under catalyst- and solvent-free conditions was reported to afford the desired compounds in excellent yields with potent pharmacological properties. The synthetic method involves the preparation of isoindolin-1-one-3-phosphonates by a ‘one-pot’ three-component reaction of 2-formylbenzoic acid with primary amines and dimethyl phosphite under solvent and catalyst free-conditions. All new compounds were characterized by by 1H NMR, 13C NMR, FT-IR and elemental analysis techniques. The synthesized compounds were screened for their antimicrobial activities against gram-positive bacterial strains (Micrococcus luteus, Listeria monocytogenes, Staphylococcus aureus and Bacillus cereus), a gram-negative bacterial strain (Salmonella typhimurium) and a fungus (Candida albicans). Compound 4a was found to be the most active against antimicrobial against L. M. luteus, L. monocytogenes and C. albicans with an inhibition zone of 35, 22 and 38 mm respectively. They were additionally also investigated for their anti-parasitical activities against Leishmania major promastigotes and amastigotes and Toxoplasma gondii in vitro. The compounds 4a,b are the most active against L. major amastigotes and promastigotes with EC50 < 1 µM. Cytotoxicity investigations of the isoindolin-1-one-3-phosphonates were conducted in two human cancer cell lines, MDA-MB-231 and MCF-7 all the compounds gave anticancer activity < 1.5 µM. We can conclude that 4a is a good drug candidate for all the biological assays, further studies for SAR detection and in vivo evaluation are highly recommended.