Background:
Colon cancer is one of the most widespread disease, the mortality rate is high due to
cancer metastasis and the development of drug resistance. In this regards, new chemotherapeutic agents with
specific mechanisms of action and significant effect on patient’s survival are the new era for the colon cancer
drug development.
Objective:
The main objective of present study was to design, synthesize of a novel series of 1,3,4-thiadiazole
derivatives (VR1 to VR35) and screen them against HT-29 human colon cancer cell line.
Method:
Newly 1,3,4-thiadiazole scaffold were designed, synthesized and further, characterized by FTIR, NMR
(1H and 13C), MS and elemental analyses. Before the synthesis, molecular dynamic simulation and ADME studies
were performed to find out the most potent lead compounds. Later, SRB assay using HT-29 cells and ELISA
assays were performed to explore activity and molecular targets of VR24 and VR27 and find out whether in
silico data had a similar pattern in the molecular level.
Results:
The results of docking study revealed that both VR24 and VR27 had interaction energy >-5 kcal/mol
with various assigned molecular targets and the ligand-protein complexes were found to be stable with IL-6. The
computational analysis of molecules showed good ADMET profiling. Later, the in vitro anticancer study was
conducted where VR24 and VR27 were found to be active against HT-29 cells (GI50<10 µM). Finally, ELISA
assays revealed that both the compounds had higher inhibition properties to various biomarker of colon cancer
like IL-6 and COX-2.
Conclusion:
Collectively, these result suggested that VR24 and VR27 inhibited the assigned molecular targets,
imparting their ameliorative effects against colon cancer. Due to these encouraging results, we concluded that
both VR24 and VR27 may be effective against colon cancer therapy in future.
QSAR and molecular docking studies of novel 2,5-distributed-1,3,4-thiadiazole derivatives containing 5-phenyl-2-furan as fungicides against Phythophthora infestans
