Synthesis and evaluation of novel benzophenone-thiazole derivatives as potent VEGF-A inhibitors

• Published in: European journal of medicinal chemistry Vol. 87; pp. 274 - 283
• Main Authors: Prashanth, T., Thirusangu, Prabhu, Vijay Avin, B.R., Lakshmi Ranganatha, V., Prabhakar, B.T., Khanum, Shaukath Ara
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 24.11.2014; Elsevier
• Subjects: Animals; Antiproliferation; Benzophenone; Benzophenones - chemical synthesis; Benzophenones - chemistry; Benzophenones - pharmacology; Cell Line, Tumor; Chemistry Techniques, Synthetic; Chemistry, Medicinal; Disease Progression; Drug Design; Humans; In vivo; Life Sciences & Biomedicine; Male; Mice; Pharmacology & Pharmacy; Science & Technology; Structure-Activity Relationship; Thiazoles; Thiazoles - chemistry; Vascular Endothelial Growth Factor A - antagonists & inhibitors; VEGF-A; Xenograft Model Antitumor Assays; Antiproliferation; DLAl; In vivo; EAC; Thiazoles; VEGF-A; Benzophenone; APOPTOSIS; ANALOGS; BEVACIZUMAB; ANTICANCER AGENTS; ANTITUMOR-ACTIVITY; CANCER; In vivo; IN-VIVO; CARCINOMA; CELL; ENDOTHELIAL GROWTH-FACTOR
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.09.069

A series of 2-(4-benzoyl-phenoxy)-N-(4-phenyl-thiazol-2-yl)-acetamides (10a–n) were synthesized by multistep reaction sequence and all the compounds were well characterized for structural elucidation. The in vitro cytotoxicity of compounds 10a–n was evaluated against EAC and DLA cell lines using trypan blue dye exclusion method. Further MTT assay and LDH release assay, followed by in vivo studies on murine model were also evaluated. The compound 10h with a methyl and fluoro groups at benzophenone moiety and methoxy group at phenyl ring was in a leading position to exhibit the promising antiproliferative effect through translational VEGF-A inhibition. A series of 2-(4-benzoyl-phenoxy)-N-(4-phenyl-thiazol-2-yl)-acetamides were synthesized and characterized, further all the new compounds were tested for their anticancer activity. [Display omitted] •Novel benzophenone-thiazole derivatives were synthesized.•In-vitro cytotoxicity of 10a–n was evaluated against EAC and DLA cell lines.•10h with methyl, fluoro and methoxy groups was in a leading position among 10a–n.•In-vivo studies are conducted on murine models.•Compound 10h exhibits the promising antiproliferative effect.