Synthesis of chalconoyl pregnenolones as antimicrobial, antidiabetic and antioxidant agents

Abstract

The steroidal tetracyclic skeleton and the chalcones are considered as privileged structures in medicinal chemistry. In this endeavour, pregnenolone, which is considered as the main precursor of the all steroid hormones, was subjected to Claisen-Schmidt condensation with differently substituted benzaldehydes to synthesise 12 steroidal chalconoids or chalconoyl pregnenolones (PC-1 to PC-12) including 7 new chalconoids. The structural confirmation of the synthesised compounds was based on their IR, ¹H- and ¹³C-NMR, as well as the HRMS data. Three different in vitro antioxidant assays such as DPPH^• (2,2-diphenyl-1-picrylhydrazyl), ABTS^•+ (2,2́-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)), and FRAP (ferric reducing antioxidant power) assays were performed to evaluate the antioxidant properties of the synthesised compounds. Compound PC-3, with hydroxy substituents in the 3- and 4- positions of the benzaldehyde moiety, exhibited the highest antioxidant properties, with comparable FRAP value and radical inhibitory capability to the standards employed. The antidiabetic potential of the compounds was evaluated through the α-glucosidase inhibitory assay; in which significant α-glucosidase inhibitory potential (with over 50% inhibition of the enzyme) was demonstrated by the majority of the synthesised compounds. The compounds were tested against six different bacterial strains to ascertain their antibacterial properties. The results of the antibacterial studies, such as zone of inhibition against the selected Gram-positive and Gram-negative bacteria and their minimum inhibitory concentration values suggest that the synthesised compounds possess promising antimicrobial properties against the bacterial strains.

Graphical abstract