Synthesis And Antitumor Activity Of BTA Derivatives

Benzotriazole is benzene and triazole heterocyclic compound with several biological and pharmacological properties. This compound and its derivatives demonstrate important pharmacological activities such as anti-inflammatory, antiviral, anti-fungal, anti-neoplastic and antidepressant activities,especially its anti-tumor activity arouses great concern. The angiogenesis is a critical process for the growth, progression, and metastases of a variety of solid tumors, which involves protein tyrosine kinase and its receptors, particularly the family of VEGF and VEGFR. Developing selective anti-tumor drugs which targeting protein tyrosine kinase such as VEGFR is one of the main trend in this field.This research consists of two parts, including synthesis and structure characterization of benzotriazole derivatives and antitumor activity test.The intermediates were synthesized with the nucleophilic substitution reaction of benzotriazoleor or 5-chlorobenzotriazole and chloroacetonitrile using Ultrasonic-Microwave method. The target compounds, a series of benzotriazole derivatives, were prepared by the condensation reaction of the synthetic intermediates and 6-chloronicotinaldehyde or 6-methoxynicotinaldehyde, respectively. Structure characterization of compounds was determined by IR, LC-MS and 1H-NMR analysis.The CCK-8 method was used to detect the anti-tumor activity of target compounds on human carcinoma VX2 cell lines, human lung cancer A549 cell lines, stomach MKN45 and MGC cell lines, respectively. The results indicated that these new benzotriazole derivatives possess good antitumor activity in vitro. Compound B2 M inhibit VX2 cell lines with IC50 1.20 μg/m L. Compound B2 N inhibit MGC cell lines with IC50 1.16 μg/m L. The IC50 values of Compound B3 M on A549 and MKN45 cell lines were 1.73 and 0.96 μg/m L, respectively.