Synthesis and anticancer activity of benzotriazole derivatives

Abstract

A series of benzotriazole (BTA) derivatives were synthesized as tyrosine protein kinase inhibitors using fragment‐based design strategy. All desired compounds were synthesized with the reaction of benzotriazole, chloroacetonitrile and aromatic aldehyde using Ultrasonic‐Microwave method and characterized by IR, 1H and 13C‐NMR, mass spectrometry (MS) and elemental analysis. The anticancer activity of these compounds was evaluated by CCK‐8 method against carcinoma VX2, lung cancer A549, stomach cancer cell lines MKN45 and MGC in vitro. The results showed that all compounds showed good antiproliferative activity. In particular, compound 2.1 showed the most prominent inhibition of VX2 cell lines with IC50 of 3.80 ± 0.75 μM. Compound 2.2 exhibited highly potent anticancer activity of stomach MGC cell lines with IC50 of 3.72 ± 0.11 μM. A549 and MKN45 cell lines were sensitive to compound 2.5 with IC50 of 5.47 ± 1.11 and 3.04 ± 0.02 μM, respectively.

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

“…According to Li et al, [ 72 ] a series of benzotriazole derivatives incorporating a pyridine scaffold was designed and synthesized utilizing a fragment‐based design technique. These derivatives were tested in vitro against the stomach cancer cell lines MKN45 and MGC, lung cancer A549, and carcinoma VX2.…”

“…With an IC 50 value of 59.72 µM, the benzotriazole 32 demonstrated antiproliferative activity against the cervical HeLa cancer cell line. [71] According to Li et al, [72] a series of benzotriazole derivatives incorporating a pyridine scaffold was designed and synthesized utilizing a fragment-based design technique. These derivatives were tested in vitro against the stomach cancer cell lines MKN45 and MGC, lung cancer A549, and carcinoma VX2.…”

Thermal Study of Two Benzotriazole Derivatives

“…It is also known as 1H-benzo[d]-1,2,3-triazole and exists in 1H-and 2H-tautomeric forms, being the 1H-form predominant over the 2Hform at room temperature (Figure 1) in both gas and solution phases (Ueno et al 2003). As a heterocyclic polyfunctional compound, benzotriazole and its derivatives are well known for their versatile biological properties, such as antifungal (Lv et al 2018) antimicrobial (Briguglio et al 2015), antiviral (Loddo et al 2015) and even antitumor agents (Li et al 2020). Also, these compounds are used in industrial applications due to their corrosion inhibiting capability in several metals (Finšgar and Milošev 2010), in which the knowledge of the corresponding stability is relevant for further studies.…”