Piperazin incorporated Schiff Base derivatives: Assessment of in vitro biological activities, metabolic enzyme inhibition properties, and molecular docking calculations

Abstract

The cytotoxic activities of the compounds were determined by the 3‐(4,5‐dimethylthiazolyl‐2)‐2,5‐diphenyltetrazolium bromide (MTT) method in human breast cancer (MCF‐7), human cervical cancer (HeLa), and mouse fibroblast (L929) cell lines. The compounds MAAS‐5 and four modified the supercoiled tertiary structure of pBR322 plasmid DNA. MAAS‐5 showed the highest cytotoxic activity in HeLa, MCF‐7, and L929 cells with IC50 values of 16.76 ± 3.22, 28.83 ± 5.61, and 2.18 ± 1.22 µM, respectively. MAAS‐3 was found to have almost the lowest cytotoxic activities with the IC50 values of 93.17 ± 9.28, 181.07 ± 11.54, and 16.86 ± 6.42 µM in HeLa, MCF‐7, and L929 cells respectively at 24 h. Moreover, the antiepileptic potentials of these compounds were investigated in this study. To this end, the effect of newly synthesized Schiff base derivatives on the enzyme activities of carbonic anhydrase I and II isozymes (human carbonic anhydrase [hCA] I and hCA II) was evaluated spectrophotometrically. The target compounds demonstrated high inhibitory activities compared with standard inhibitors with Ki values in the range of 4.54 ± 0.86–15.46 ± 8.65 nM for hCA I (Ki value for standard inhibitor = 12.08 ± 2.00 nM), 1.09 ± 0.32–29.94 ± 0.82 nM for hCA II (Ki value for standard inhibitor = 18.22 ± 4.90 nM). Finally, the activities of the compounds were compared with the Gaussian programme in the B3lyp, HF, M062X base sets with 6‐31++G (d,p) levels. In addition, the activities of five compounds against various breast cancer proteins and hCA I and II were compared with molecular docking calculations. Also, absorption, distribution, metabolism, excretion, and toxicity analysis was performed to investigate the possibility of using five compounds as drug candidates.

Breast cancer Properties of Extract of Artemisia absinthium

“…[20] was used for these calculations. Several modules, including protein preparation [21,22], LigPrep [23,24], and Glide ligand docking [25,26] were employed in the molecular docking calculations. The OPLS4 method was used for all calculations.…”

Breast cancer Properties of Extract of Ceratonia siliqua

“…The Maestro Molecular modeling platform (version 12.8) by Schrödinger [14] was used for these calculations. Several modules, including protein preparation [15,16], LigPrep [17,18], and Glide ligand docking [19,20] were employed in the molecular docking calculations. The OPLS4 method was used for all calculations.…”