4-aryl/heteroaryl-4H-fused Pyrans as Anti-proliferative Agents: Design, Synthesis and Biological Evaluation

The current study is focused on the design and synthesis of 4-aryl/heteroaryl-4H-fused pyrans as anti-proliferative agents. All the synthesized molecules were screened against a panel of human carcinoma cell lines.

Significant inhibition was exhibited by the compounds against HCT-116 (Colon) and PC-3 (Prostate) cell lines while A-549 (Lung) cell lines, MiaPaCa-2 (Pancreatic) cell lines and HL-60 (Leukemia Cancer) cell lines were almost resistant to the exposure of the test compounds. Compound FP-(v)n displayed noteworthy cytotoxicity towards HCT-116 malignant cells with the IC50 value of 0.67 µM. It induces apoptosis as revealed by several biological endpoints like apoptotic body formation, through DAPI staining, phase contrast microscopy and mitochondrial membrane potential loss. Moreover FP-(v)n is a potent apoptotic inducer confirmed by cell cycle arrest and ROS generation. The cell phase distribution studies indicate an augment from 4.94 % (control sample) to 39.68 % (sample treated with 1.5 µM compound FP-(v)n) in the apoptotic population. Compound FP-(v)n inhibits the tumor growth in Ehrlich ascites carcinoma (EAC), Ehrlich Tumor (ET, solid) and sarcoma-180 (solid) mice models. Additionally, it was established to be non-toxic at maximum tolerated dose of 1000 mg/kg in acute oral toxicity in Swiss-albino mice.

The current study provides an insight into anti-cancer potential of FP-(v)n, which might be valuable in the treatment of tumor.