New N-(1,3,4-thiadiazol-2-yl)furan-2-carboxamide derivatives as potential inhibitors of the VEGFR-2

The present study reports the synthesis and biological evaluation of a new series of novel N-(1,3,4-thiadiazol-2yl)furan-2-carboxamide derivatives. The reactions were executed under both conventional and microwave irradiation conditions. An enhancement in the synthetic yields and rates was observed when the reactions were carried out under the microwave compared with the classical conditions. The structures of the products were ascertained by different analytical and spectral analyses. The antiproliferative activities were evaluated against three human epithelial cell lines; breast (MCF-7), colon (HCT-116), and prostate (PC-3) using MTT assay technique and doxorubicin was utilized as a reference drug. Besides, molecular docking studies were also performed and the vascular endothelial growth factor recptor-2 (VEGFR-2) was identified as a potential molecular target. Compounds 6, 7, 11a, 11b, 12, 14, and 16 showed promising antiproliferative activity against the three cancer cell lines investigated. Compounds 2 and 15b had significant antiproliferative activities against only colon and breast cells but not against the prostate cells. All the active antiproliferative compounds were highly selective. All the active antiproliferative compounds were good inhibitors of the VEGFR-2 at 7.4-11.5 nM compared with Pazopanib. Compound 7 with the most favorable orientation to the VEGFR-2 from the docking studies, was also the best inhibitor of the receptor. The antiproliferative activity of these compounds is in partial caused by their ability to inhibit the VEGFR-2 and since other molecular targets were not examined, other possibilities cannot be ruled out.

Automated summary

This study synthesized a series of N-(1,3,4-thiadiazol-2yl)furan-2-carboxamide derivatives and found higher yields and rates under microwave conditions compared to traditional methods. The antiproliferative activities of these compounds were assessed, showing promising results against three cancer cell lines and VEGFR-2 as a potential molecular target. Some compounds exhibited significant antiproliferative activity, with Compound 7 identified as the best inhibitor of VEGFR-2.