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

Author(s): Dinesh Kumar*, Gurpreet Singh, Pooja Sharma, Arem Qayum, Girish Mahajan, M.J. Mintoo, Shashank Kumar Singh, Dilip Manikrao Mondhe, P.M.S. Bedi, Subheet K. Jain, Girish Kumar Gupta.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 18 , Issue 1 , 2018

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Abstract:

Aims: 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.

Description: 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.

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

Keywords: Apoptosis, pyrans, cytotoxicity, cell lines, cell cycle, sarcoma-180, acute toxicity, anti-cancer efficacy.

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Article Details

VOLUME: 18
ISSUE: 1
Year: 2018
Page: [57 - 73]
Pages: 17
DOI: 10.2174/1871520617666170918143911

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