Antiangiogenic Activity of 4–Chloro–Phenyl–Carbothioamide Derivatives In Ex Vivo‏ ‏and In Vitro Experimental Study

Angiogenesis is a crucial and critical ‎process in growth and development ‎that ‎has received ‎study attention in recent decades.‎ Angiogenesis inhibitors are one of the cornerstones of modern ‎anticancer treatments, tumour develop resistance to drugs rapidly, thus providing new agents is ‎crucial for patient’s survival.‎ The study investigated the effect of different concentrations of the novel ‎4–chloro–phenyl–‎carbothioamide derivative using different angiogenesis assays.‎ The present study examined the potential antiangiogenic, antioxidant, and ‎cytotoxic properties of a carbothioamide indole derivative and assessed VEGF gene expression.‎ The tested indole derivative's antiangiogenic efficacy was assessed using the ex-vivo rat ‎aorta ring (RAR) assay. The DPPH test for scavenging activity was utilized to clarify the most ‎likely cause of its antiangiogenic action. The MTT assay assessed the proliferation of the HUVEC ‎cell line while the expression of the VEGF gene in the colon cancer (HCT116) cell line was ‎analysed.‎ The evaluated drug exhibited antiangiogenic efficacy with an IC50 value of 17.99µg/ml in ‎the RAR assay. The drug successfully reduced the DPPH free radical in a concentration-dependent ‎manner (IC50 = 100.30 µg/ml). The evaluated drug exhibited negligible to non-toxic effects on the ‎HUVEC cell line, with an IC50 value of 733.60 μg/ml. It significantly downregulates the VEGF ‎gene expression in HCT116 cells at 400 µg/ml.‎ In conclusion, the 2-NHC compound exhibited significant antioxidant and anti-angiogenesis ‎effects with minimum toxicity against normal human cells. 2-NHC appears to downregulate the ‎VEGF gene expression in colon cancer cell lines.