Design, Synthesis, and Antipoliferative Activities of Novel Substituted Imidazole-Thione Linked Benzotriazole Derivatives

Abstract

A new series of benzotriazole moiety bearing substituted imidazol-2-thiones at N1 has been designed, synthesized and evaluated for in vitro anticancer activity against the different cancer cell lines MCF-7(breast cancer), HL-60 (Human promyelocytic leukemia), and HCT-116 (colon cancer). Most of the benzotriazole analogues exhibited promising antiproliferative activity against tested cancer cell lines. Among all the synthesized compounds, BI9 showed potent activity against the cancer cell lines such as MCF-7, HL-60 and HCT-116 with IC50 3.57, 0.40 and 2.63 µM, respectively. Compound BI9 was taken up for elaborate biological studies and the HL-60 cells in the cell cycle were arrested in G2/M phase. Compound BI9 showed remarkable inhibition of tubulin polymerization with the colchicine binding site of tubulin. In addition, compound BI9 promoted apoptosis by regulating the expression of pro-apoptotic protein BAX and anti-apoptotic proteins Bcl-2. These results provide guidance for further rational development of potent tubulin polymerization inhibitors for the treatment of cancer.

Nitrogen Containing Heterocycles as Anticancer Agents: A Medicinal Chemistry Perspective

“…Anticancer activity screening results revealed that compound 48 was the most promising anticancer agent having IC 50 values of 3.57, 0.4, 2.63 and 118.9 µM, respectively. CA-4 was used as a reference drug with IC 50 values of 0.58, 0.77, 0.24, and 13.6 µM, respectively[ 165 ]. Quinazoline-based imidazole derivatives were synthesized and screened for their anticancer activity against epidermal growth factor receptor (EGFR) and HT-29 cell lines (normoxic and hypoxic conditions) by Kumar et al (2022).…”

Design, Synthesis, Antimicrobial Evaluation of Novel 2‐Oxo‐4‐Substituted Aryl‐Azetidine Benzotriazole Derivatives**

“…Benzotriazole exhibiting different pharmacological activities. [21][22][23][24][25][26][27][28] Year Benzotriazole derivative synthesized Authors/Investigator Reported activity Ref.…”

“…Moreover, azetidine-2-one structural moiety has almost recognized as therapeutic potential. [20] Benzotriazole and its Pharmacological Activity [21][22][23][24][25][26][27][28] Also act as strong vasodilator, hypotensive, antibacterial, antifungal, and antiparasitic properties were demonstrated by benzofuran derivatives. [29] Different nitrogen-containing spiroheterocyclic derivatives were isolated from natural sources and prepared synthetically such as from frog neurotoxin example histrionicotoxin 283 A, shelf fish toxins includes spirolides etc.…”

Benzotriazole scaffold: An overview of antiproliferative potential, mechanisms of action, and structure–activity relationships

“…These results indicated that the 3,4,5‐trimethoxyphenyl ring of CA‐4 could be adequately replaced by the substituted benzotriazole ring. [ 48 ]…”