Abstract

Synthesis and Pharmacological Evaluation of Pyrazoline and Pyrimidine Analogs of Combretastatin-A4 as Anticancer, Anti-inflammatory and Antioxidant Agents

Highlights

  • C ANCER is a serious and dreadful disease, difficult to alleviate

  • It is clearly understood that cancer is a disease of the cell cycle, a complex process regulated by four consecutive phases: gap 1 (G1), DNA-synthesis (S), gap 2 (G2) and mitosis (M)

  • One such approach is to target microtubule, a dynamic structure that elongates or shrinks with the addition or exclusion of tubulin proteins.[3]. It is an important cytoskeletal filament crisscrossing the cytoplasm of all the eukaryotic cells and perform a vital cellular function such as separation of the chromosome during mitosis, shape maintenance and vesicle transport

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Summary

Introduction

C ANCER is a serious and dreadful disease, difficult to alleviate. It is clearly understood that cancer is a disease of the cell cycle, a complex process regulated by four consecutive phases: gap 1 (G1), DNA-synthesis (S), gap 2 (G2) and mitosis (M). Understanding the molecular mechanism involved in cancers can help to procure novel anticancer agent One such approach is to target microtubule, a dynamic structure that elongates or shrinks with the addition or exclusion of tubulin proteins.[3] It is an important cytoskeletal filament crisscrossing the cytoplasm of all the eukaryotic cells and perform a vital cellular function such as separation of the chromosome during mitosis, shape maintenance and vesicle transport. Combretastatin-A4 (1, CA-4, Figure 1) in particular, is an effective antivascular and antimitotic agent, which inhibit tubulin polymerization by binding to colchicine binding site.[5] lack of microtubule in the metaphase of the cell cycle halts mitotic spindle formation.[6] Besides, it alters endothelial cell structure and vascular permeability, resulting in vascular collapse and tumor necrosis.[2,7] Despite the potent cytotoxic and anti-tubulin in vitro efficacy, CA-4 does come with

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