Experimental and theoretical investigation of synthesized pregnenolone derivatives via palladium catalyzed cross coupling reactions, their anticancer activity against lung cancer cells

Abstract

In the current research work synthesis of novel steroids, PGLCROBB, PGLCROMBT, and PGLCROB are being reported employing palladium catalyzed Mizoroki-Heck reaction. Structure elucidation of all the synthesized compounds was done by 1H NMR, 13C NMR, IR, and mass spectrometry. These prodrugs PGL, PGLCRO, PGLCROBB, PGLCROMBT, and PGLCROB were tested on human lung cancer cell line (A549). The results were very promising as PGLCROB has shown significant anticancer activity against lung cancer cells. In order to look into the structural stability and electronic feature analyses, quantum chemical calculations have been performed using the DFT approach. To spot, describe, and estimate competently the weak C-H⋯O H-bonding and H⋯H (conventional) as well as C⋯H (unconventional) non-covalent interactions (NCIs) involved therein, the Bader's QTAIM and NCI-plot have also been executed. The H⋯H bond paths range from 2.021 Å to 2.039 Å however the C⋯H bond paths fall between 2.806 Å and 2.871 Å and such type of interactions demonstrate all the characteristics of a closed-shell interaction. The analyzed chemical reactivity mainly emphasized for PGLCRO, PGLCROB, PGLCROBB and PGLCROMBT systems shows that the PGLCROB (with a very marginal difference with the PGLCROBB) is chemically more reactive (highly sensitive) species among all steroids. This work represents another instance of the utilization and successful application of the concept of bond path and the QTAIM.