N-(Benzo[d]thiazol-2-yl)benzamide and its chlorinated isomers: synthesis, NMR, FT-IR, UV-visible, BSA- and DNA-binding, DFT, molecular docking, and pharmacokinetic profiles

Abstract

N-(Benzo[d]thiazol-2-yl)benzamide and its derivatives are well known for their diverse pharmacological activities, including antimicrobial, anti-inflammatory, and anticancer properties, making their fusion a promising strategy for novel therapeutic agents. Our synthetic approach involved the condensation of 2-aminobenzothiazole with various substituted benzoyl chlorides. All synthesized compounds were fully characterized using spectroscopic techniques, including ¹H NMR, ¹³C NMR, IR, and UV. Preliminary biological screening revealed that several derivatives exhibited a promising diverse range of pharmacological activities in the areas of life sciences and biology. Also, the recorded FT-IR, NMR, and UV-visible spectroscopic data of BA and chlorinated-BA isomers were compared with those of computational counterparts obtained from B3LYP/6-311G** level simulations. log P and log S simulations revealed that the BA compound would be more soluble in water and thus less lipophilic, whereas the chlorine-substituted isomers would be less soluble in water. Also, the iLOGP values of the compounds were calculated in the optimal range of −0.7 and +5.0, which indicated the potential for oral bioavailability. The BOILED-Egg model implied that BA and its isomers would have BBB penetration passively since all of them were located in the yolk region of the BOILED-Egg. FMO analyses implied that the BA compound would be less capable of charge transfer and gain more stability via back-donation, more than the chlorinated BA isomers. The characterized molecules were analyzed for BSA- and DNA-binding properties via UV-visible spectroscopy by the Benesi–Hildebrand method and fluorescence spectroscopy by the Stern–Volmer method. The best binding constants for both BSA and DNA binding were determined for 2CBA as 4.23 × 10⁴ and 2.07 × 10⁴, respectively. 4CBA has the best Stern–Volmer constants for BSA and DNA binding with values of 2.43 × 10² and 1.52 × 10³, respectively. On the other hand, the highest binding number was determined for BA in BSA-binding experiments, while 4CBA has a binding number of 1.274 for DNA-binding evaluation. Additionally, BSA- and DNA-binding properties were also evaluated with molecular docking methods against BSA and DNA target crystals. According to both computational and experimental results, 2CBA has the best binding potential.