Design, Synthesis and Antitumor Activity of Novel pyran-functionalized Uracil Derivatives: Docking Studies

Abstract

Aim: Synthesis of novel pyran-based uracils that may have potent antitumor activity against hepatocellular carcinoma HepG2 and ovarian cancer SKOV3 cell lines. Materials & methods: Novel pyran-based uracils were synthesized and their anticancer activity was assessed using methyl thiazolyl tetrazolium and wound-healing assays to detect their cytotoxicity and their antiproliferative and antimigratory activities. Results: Compounds 3, 5, 6, 7, 8, 9, 10, 11 and 13 significantly inhibited cell proliferation of the HepG2 cell line. Compounds 7, 8, 9 and 13 significantly inhibited the proliferation of SKOV3 cells, which was also proven through docking studies with topoisomerase I. Conclusion: The molecular docking analysis revealed that 7 and 9 are two major compounds found to possess higher degrees of interaction with DNA gyrase.

Uracil: A Pharmacophore with Diverse Biological Potential

“…[15,16] The 5-chloro uracil linked with pyrazolo [1,5a][1, 3,5] triazines are used as potent thymidine phosphorylase inhibitors. [17] Uracil derivatives having thienyl and furanyl moiety displays remarkable activity against herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV). [18] 5-fluorodeoxyuridine (FdUrd), often known as floxuridine, is an anticancer drug predominantly used to treat gastrointestinal cancer, notably colorectal cancer.…”

“…5‐fluoro, 5‐iodouracils and 6‐aminouracils are known to have profound antitumour activity [15,16] . The 5‐chloro uracil linked with pyrazolo [1,5‐a][1,3,5] triazines are used as potent thymidine phosphorylase inhibitors [17] . Uracil derivatives having thienyl and furanyl moiety displays remarkable activity against herpes simplex virus type 1 (HSV‐1) and varicella‐zoster virus (VZV) [18] .…”

Novel Thiazole Derivatives Containing Imidazole and Furan Scaffold: Design, Synthesis, Molecular Docking, Antibacterial, and Antioxidant Evaluation

“…Moreover, there are numerous pharmaceuticals that contain imidazole and thiazole components (Figure 1). Given the multitude of advantages and as a logical extension of my efforts [38][39][40][41][42][43], in this study, I describe the creation of new thiazole compounds that have a 2-(furan-2-yl)-1H-imidazole component, which acts as an antibacterial agent. Given the multitude of advantages and as a logical extension of my efforts [38][39][40][41][42][43], in this study, I describe the creation of new thiazole compounds that have a 2-(furan-2-yl)-1Himidazole component, which acts as an antibacterial agent.…”

Novel Hydrazide Hydrazone Derivatives as Antimicrobial Agents: Design, Synthesis, and Molecular Dynamics

“…These hydrazones have been developed as antimicrobial agents. This research built upon previous work and took into account the advantages associated with these compounds [27][28][29][30][31][32].…”