Synthesis, anti HIV-1 reverse transcriptase and cytotoxic activity of phthalimide derivatives

Abstract

The novel phthalimide derivatives were designed and synthesized by modifying of the phthalimide structures based on the three-dimensional quantitative structure-activity relationship (3D QSAR), comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies. These derivatives were synthesized using phthalimide and substituted benzyl halide in the presence potassium hydroxide. Six newly synthesized compounds were evaluated for HIV-1 reverse transcriptase inhibitory activity by radioactivity assay at concentration 200 ug/mL using poly(rA).oligo(dT) as template-primer, methyl- [3H]dTTP as substrate and doxorubicin (1.25 mM) as positive control. The synthesized compounds showed low inhibitory activity in the range of 7.9-22.9 % inhibition. Since infection with HIV-1 is associated with an increased risk of developing certain types of cancer, the previously and newly synthesized phthalimide derivatives have been subjected to cytotoxic activity testing using MTT colorimetric method against the cancer cell lines KB and HeLa and normal vero cell line. 1- Phthalimidomethyl-4-tert-butylbenzene, compound 36 demonstrated promising cytotoxic activity that was less toxic to normal cells.