Synthesis, Structural, Computational, and Antiproliferative Activity Studies of New Steroidal Tetrazole Derivatives

Herein, we report the synthesis of five new tetrazole-tethered steroids ( 5 -9 ), analogues of the prostate cancer drug abiraterone. All newly prepared compounds were characterized by H-1 and C-13 NMR spectroscopy and high-resolution mass spectrometry, while compounds 6 and 7 were also analyzed by single-crystal X-ray diffraction. Intermolecular interactions observed in the crystals were examined by Hirshfeld surface analysis, 2D fingerprint plots, and noncovalent interaction analysis. Maps of molecular electrostatic potential were obtained by DFT calculations for 5 -9 . Additionally, all of the analogues were subjected to frontier orbital analysis. In antiproliferative activity assays, compounds 5, 7, and 9 were shown to exhibit antiproliferative activity toward the PC-3 cell line in the low-micromolar IC50 range. Similarly high activity was observed of 5 toward MCF-7, of 7-9 toward MDA-MB-231, of 5 and 7 toward HT-29, and of 6 toward A549, with no observed cytotoxicity toward the noncancerous MRC-5 cell line. (C)& nbsp;2022 Elsevier B.V. All rights reserved.