LAUSR

Abstract Co-crystals are emerging as members of supramolecular family having particular practical and fundamental significance for chemists, crystallographers, pharmaceutical scientists, and theoreticians. The presented study is focused to synthesize anti-cancer co-crystals of commercially available nandrolone (1), a synthetic anabolic-androgenic steroidal drug. Co-crystallization is done using economical and green grinding and reflux methods to obtain nandrolone (Nan): salicylic acid (Sal) and nandrolone (Nan): 3-amino-1,2,4-triazole (Triz) co-crystals, in 2:1 and 1:1 stoichiometric ratios, respectively. The structural analysis and characterization were carried out using single-crystal X-ray diffraction, and vibrational spectroscopy. Nandrolone (1) crystallizes in monoclinic P21 space group, while the co-crystal-I (Nan:Sal) and co-crystal-II (Nan:Triz), co-crystallized in the orthorhombic P212121 space group. The intermolecular hydrogen bonds O—H•••O, C—H•••O, N—H•••O, O—H•••N, and N—H•••N between the active pharmaceutical ingredient (nandrolone) and co-formers (salicylic acid, and 3-amino-1,2,4-triazole) stabilize the structures of co-crystals. In vibrational spectroscopy of co-crystal-I (Nan:Sal), the blue shifts in stretching frequencies of hydroxyl group from 3417.9 cm−1 to 3427.8 cm−1 further supported the hydrogen bond interactions between API and co-former. Similarly, in co-crystal-II (Nan:Triz) the NH2 stretching frequency from 3331.4– 3413.4 cm−1 to 3312.7 cm−1, supported the interaction of NH2 with API via intermolecular interaction. Nandrolone (1) and both co-crystals were found to be non-cytotoxic against 3T3 normal fibroblast cell line. Nandrolone (IC50 = 1.0 ± 0.1 µM), co-crystal-I (Nan:Sal) (IC50 = 1.6 ± 0.3 µM) and -II (Nan:Triz) (IC50 = 1.8 ± 0.1 µM) showed anti-cancer potential against cervical cancer HeLa cell line. While doxorubicin (IC50 = 1.2 ± 0.2 µM) was used as standard tested compound. SYNOPSIS Two new non-cytotoxic co-crystals of synthetic anabolic-androgenic steroidal drug nandrolone (Nan) with pharmaceutically acceptable salicylic acid (Sal), and triazole (Triz) were synthesized and their structures were elucidated using single-crystal X-ray diffraction, and vibrational spectroscopy. Quantitative analysis of —OH and —NH2 intermolecular interactions between API and co-former by Hirshfeld surface analysis further supported the role of various functionalities towards the stability of co-crystals. Both co-crystals were found to be non-cytotoxic against 3T3 normal fibroblast cell line. Co-crystal-I (Nan:Sal) and co-crystal-II (Nan:Triz) were found to be selectively active against HeLa cancer cell line (IC50 = 1.6 ± 0.3 µM), (IC50 = 1.8 ± 0.1 µM).