Synthesis, biological evaluation and docking studies of 1,2,4-oxadiazole linked 5-fluorouracil derivatives as anticancer agents

Abstract

Background 1,2,4-oxadiazole derivatives exhibited significant anti-cancer activity when they were evaluated, against human cancer cell lines. They also showed anti-inflammatory, analgesic, diabetic, immunosuppressive, α,β3-receptor antagonist, antimicrobial, anti-helminthic, histamine-H3 and antiparasitic properties. A pyrimidine analog, 5 fluoro-uracil is a chemotherapeutic drug used for treating multiple solid malignant tumors. But its application is limited, as it has side effects like low bioavailability and high toxicity. Molecular docking is an exemplary tool, helps in identifying target and designing a drug containing high bio-availability and minimum toxicity. Results A set of 1,2,4-oxadiazole linked 5-fluoruracil derivatives (7a–j) were synthesized and their structures were confirmed by 1HNMR, 13CNMR and Mass spectral analysis. Further, these compounds were investigated for their anticancer activity towards a panel of four human cancer cell lines such as (MCF-7, MDA MB-231), lung cancer (A549) and prostate cancer (DU-145) by using MTT method. Among them, compounds 7a, 7b, 7c, 7d and 7i demonstrated more promising anticancer activity than standard. Conclusion Synthesized derivatives (7a–j) of 1,2,4-oxadiazole linked 5-fluorouracil and investigated for their anticancer activity towards a panel of four human cancer cell lines.

Synthesis, molecular docking study and anticancer activity of novel 1,3,4-oxadiazole derivatives as potential tubulin inhibitors

“…In recent years, heterocyclic rings with nitrogen atoms have become quite important in medicinal chemistry. They are regarded as essential models for the creation of novel therapeutics [ 11 ]. Oxadiazoles holds a special place among these privileged moieties because of their function in the creation of anticancer medications [ 12 , 13 ].…”

Dihydroartemisinin and zerumbone esters of ataluren and its analogs as anticancer agents and EGFR inhibitors

“…3 In addition, 1,3,4-oxadiazoles and 1,2,4-oxadiazoles also demonstrate a wide spectrum of biological activities, such as antimicrobial, anticancer, antiinflammatory, and antiviral activities. [4][5][6][7] Furthermore, ataluren (2) (Figure 1), a member of the 1,2,4-oxadiazole family, holds a special pharmacological property applied to the treatment of Duchenne muscular dystrophy (DMD) disease. 8 In pathology, DMD is a muscle-wasting condition that causes progressive muscle weakness, and ataluren is approved as a specific drug for this disease.…”

“…9 In pharmaceutical chemistry and drug development, esters are often used as prodrugs with the purpose of enhancing some properties of parent drugs, such as solubility, oral adsorption, membrane permeability, duration of action, and reducing side effects. [10][11][12][13][14] Some typical examples given approve the structural diversity of esters in commercially available medicines in the world, including aspirin (3), enalapril (4), nitazoxanide (5), and artesunate (6) (Figure 1). Structurally, esters are composed of two components, including carboxylic acids and alcohols/phenols, that are usually present in natural compounds or their derivatives; therefore, natural alcohols/phenols or carboxylic acids are always preferred compounds for ester formation.…”

Enzyme kinetics of deoxyuridine triphosphatase from western corn rootworm

“…Therefore, for example, the thymidylate synthesis pathway is the point of action for several anticancer agents in human [12][13][14][15]. Redundancy of the supply of the substrate dUMP, however, often limits the anticancer effect of pyrimidine antagonists [16,17]. 5-Fluorouracil (5FU) is a TS inhibitor and used for cancer therapy where a large amount of accumulated dUMP leads to uracil misincorporation [18,19].…”