Molecular modeling of 3-chloro-3-phenylquinoline-2,4-dione, crystal structure and cytotoxic activity for developments in a potential new drug

3-Chloro-3-phenylquinoline-2,4-dione (2) is an intermediate product in the synthesis of 1-phenyl-2H,6H- imidazo[1,5-c]quinazoline-3,5-dione (PhIC). PhIC, its intermediates, and derivatives belong to quinolines or quinazolines -heterocyclic compounds with biological activity. However, only compound 2 contains nitrogen and chlorine atoms in the structure and has the most probability of having anticancer proper-ties. In this work, the crystal structure of compound 2 was investigated by X-Ray crystallography and the molecular modeling was made by DFT methods. The cytotoxic activities of 3-hydroxy-3-phenylquinoline-2,4-dione, 3-chloro-3-phenylquinoline-2,4-dione and 3-amino-3-phenylquinoline-2,4-dione, respectively compounds 1, 2, and 3 (with quinoline ring), and 2-(2-hydroxypropyl)-6-H-imidazo[1,5-c]quinazoline-3,5- dione - compound 4 (with imidazoquinoline ring) against the cell lines: mouse fibroblast L929 and hu-man gastric adenocarcinoma cells (AGS) were tested. The crystal structure of compound 2 was established and the intermolecular interactions were described. Only one pair of enantiomers was found in the unit cell, whereas molecular modeling showed two pairs of enantiomers AA' and BB' are stable. The enan-tiomer pairs can transform into each other to better spatial packing in the crystal. Compounds 2 and 4 show high cytotoxic activity against the L929 line at the concentration range 0.05- 50 mu g/ml, and AGS cells (0.1- 50 mu g/ml). When bound to an appropriate carrier to deliver the compound directly to neoplas-tic cells, their use as anti-neoplastic substances cannot be excluded.(c) 2023 Elsevier B.V. All rights reserved.