Design, Synthesis, and Biological Evaluation of 2‐(4‐Aminophenyl)benzothiazole Analogues as Antiproliferative Agents

Abstract

A series of 28 novel 2‐(4‐aminophenyl)benzothiazole analogues have been synthesized and characterized using various analytical techniques like 1H NMR, 13C NMR, electrospray ionization mass spectrometry, and IR and bioevaluated for their antiproliferative activity over a group of three human cancer cell lines, namely, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MDA‐MB‐231), using sulforhodamine B assay method. Few synthesized molecules (5a, 5c, 5d, 5f, 7b, and 7j) displayed effective growth inhibition (GI50) activity against the tested human cancer cell lines at lower micromolar concentration (GI50) values in the range 0.2–1.7 μM. Noticeably, compound 7b exhibited reasonable activity in all three cancer cell lines in the GI50 range 0.55–1.2 μM. Further, when 7b was screened for tubulin polymerization inhibition, it exhibited more than 55% inhibition at concentration of 5.0 μM. The molecular docking simulations supported the molecular interactions of the derivatives with the targeted receptor. These derivatives may serve as lead structures for development of potential anticancer drug candidates, and 7b might act as a potential microtubule polymerization inhibitor.

Radical Arylation of Triphenyl Phosphite Catalyzed by Salicylic Acid: Mechanistic Investigations and Synthetic Applications

“…Aniline 1ac was synthesized by minor modifications of a reported procedure. 43 Into a pressure tube equipped with a magnetic stirrer were added 4-aminobenzoic acid (1.37 g, 10.0 mmol, 1 equiv) and polyphosphoric acid (4 g). The reaction mixture was gently heated to obtain a homogeneous mixture, before adding 2-aminophenol (1.04 mL, 10.0 mmol, 1 equiv).…”

“…The reaction mixture was then diluted with EtOAc (25 mL), transferred to a round-bottom flask, and the solvent was evaporated in vacuo. The crude mixture was purified by flash column chromatography on silica gel from hexane 100% to 90:10 hexane/EtOAc obtaining the TEMPO-adduct as a white amorphous solid (26.7 mg, 0.096 mmol, 32%): TLC (hexane/EtOAc 90:10) R f 0.65; 1 (43), 149 (20), 125 (100), 97 (40).…”

“…Aniline 1ac was synthesized by minor modifications of a reported procedure. 43 Into a pressure tube equipped with a magnetic stirrer were added 4-aminobenzoic acid (1.37 g, 10.0 mmol, 1 equiv.) and polyphosphoric acid (4 g).…”

Novel Para-Aminobenzoic Acid Analogs and Their Potential Therapeutic Applications

“…The synthesis of benzo[d]thiazolyl-phenyl-chloroacetamide was achieved by treating aminophenyl-benzothiazole with haloacetyl chloride in the presence of triethylamine, and further reacting with piperazines-based compounds at 100 • C produced the end products. Benzo[d]thiazolyl-propynyl-aniline was synthesized by treating aminophenylbenzothiazole with propargyl bromide [84].…”

Design, synthesis, biological evaluation, and in silico studies of 2‐aminobenzothiazole derivatives as potent PI3Kα inhibitors

“…For example, In 2019, Diao et al [18] have reported compound V, which demonstrated strong anticancer activity against HCT116, HeLa, MCF-7, PC-3, and MDA-MB-231 cancer cell lines with IC 50 0.70, 10.91, 0.45, 1.80, and 0.92 µM, respectively. Narva et al [19] in 2018 have reported a novel series of 2-(4-aminophenyl) benzothiazole analogs and found 4-(benzo[d]thiazol-2-yl)-N-{ [1-(3-methoxyphenyl)-1H-1,2,3-triazol-4-yl]methyl}aniline (VI) most active against HeLa cancer cell line; it showed excellent inhibitory activity with an IC 50 value of 0.98 µM. Lee et al [20] have reported derivatives of 2-aminobenzothiazole with potent anticancer activity.…”