Synthesis, characterization and in silico screening of potential biological activity of 17α-ethynyl-3β, 17β, 19-trihydroxyandrost-5-en acetylated derivatives

Abstract The synthesis of 17α-ethynyl-3β,17β,19-trihydroxyandrost-5-en derivatives diacetylated at position 3- and 19- (2a), or monoacetylated at position 3 (2b) or 19 (2c), obtained by Grignard reaction over 3β,19-diacetoxyandrost-5-en-17-one (1a), is described. The characterization (NMR, IR, HRMS) and structural analysis of the target molecules are presented, with support from SXRD diffraction studies for three derivatives and DFT computations at the B3LYP/6-31+G(d,p) level of theory, featuring Hirshfeld surface analyses and ESP computations. The impact of these structural derivatizations was further analyzed employing a theoretical evaluation of the potential biological activity of these molecules through the PASS test, envisioning a potential use of these new steroids as lipid metabolism regulators and anti-inflammatory agents.