Abstract

MOLECULAR DESCRIPTORS AND BIOACTIVITY SCORES OF 6- SUBSTITUTED BENZIMIDAZOLE-2-CARBAMATES AS POTENTIAL ANTICANCER AGENTS

Malathi Raghunath*, Anoop Singh and C.L. Viswanathan

ABSTRACT

ABSTRACT A set of 6-substituted benzimidazole-2-carbamates were synthesized and tested for their in vitro antitumor activity on four human cancer cell lines such as A549 (lung), COLO 205 (colon), SK-MEL-2 (melanoma) and JURKAT (leukemia). Significant antitumor activity was obtained for these compounds in in vitro cytotoxicity assays. Therefore these compounds were taken for determination of their molecular properties and prediction of bioactivity to assess the drug likeness and oral bioavailability based on Lipinski’s rule of five. The software used for analyzing various molecular descriptors based on chemical structure of 6-substituted benzimidazole-2-carbamates was Molinspiration cheminformatics software accessed online and Chemdraw ultra software v 7.0. All compounds met the criteria for Lipinski’s rule with respect to molecular weight, number of hydrogen bond donors, number of hydrogen bond acceptors and n-octanol water partition coefficient (C log P). Other molecular properties examined were molecular polar surface area (TPSA), number of rotatable bonds, number of atoms and molar refractivity. TPSA was found to be below 140 Å2 for all compounds. The number of rotatable bonds was found to be < 10 and number of atoms in each molecule was found to be < 30. The predicted bioactivity scores of these compounds were found to be similar to other known anticancer agents such as nocodazole and imidazopyridazine carbamates. The data obtained can thus be useful in developing newer antitumor agents belonging to class of benzimidazole-2-carbamates.

Keywords: antitumor activity, molecular descriptors, oral bioavailability, benzimidazole- 2-carbamates, imidazopyridazine carbamates.