Nucleobase-Based Barbiturates: Their Protective Effect against DNA Damage Induced by Bleomycin-Iron, Antioxidant, and Lymphocyte Transformation Assay

Abstract

A number of nucleobase-based barbiturates have been synthesized by combination of nucleic acid bases and heterocyclic amines and barbituric acid derivatives through green and efficient multicomponent route and one pot reaction. This approach was accomplished efficiently using aqueous medium to give the corresponding products in high yield. The newly synthesized compounds were characterized by spectral analysis (FT-IR, 1H NMR, 13C NMR, HMBC, and UV spectroscopy) and elemental analysis. Representative of all synthesized compounds was tested and evaluated for antioxidant, bleomycin-dependent DNA damage, and Lymphocyte Transformation studies. Compounds TBC > TBA > TBG showed highest lymphocyte transformation assay, TBC > TBA > BG showed inhibitory antioxidant activity using ABTS methods, and TBC > BPA > BAMT > TBA > 1, 3 -TBA manifested the best protective effect against DNA damage induced by bleomycin.

Barbiturate derivatives for managing multifaceted oncogenic pathways: A mini review

“…The Lymphocyte transformation assay for analyzing the specific immune response and mitogenic effect of barbiturate‐nucleobase conjugates on T‐lymphocytes displayed a significant reduction in the transformation of lymphocytes thereby indicating the protective effect against DNA damage. The result concluded barbiturate pharmacophore as hydrogen bonding and electron donating domain, while acting as bioisostere of pyrimidine moiety (Dhorajiya, Dholakia, et al, 2014).…”

Enamino Barbiturates as Antiproliferative and Antimicrobial Agents: Studies on Synthesis, Biological Activities, and Molecular Modeling

“…identified a series of thiobarbituarte‐based s–triazine hydrazone derivatives as dual‐effective inhibitors against four cancer cell lines, A549, HepG2, HCT‐116, and MCF‐7. Of these derivatives, the compound represented in Figure 1b shows the most potent activity against the MCF‐7 cancer cell line [13] . In addition, the recent studies demonstrated that novel barbituric acid derivatives inhibited the development of hepatocellular carcinoma, which is the most common type of primary liver cancer as shown in Figure 1c [14‐15] …”

“…The SAR analysis indicated the importance of the nucleobase‐based functional groups in barbiturate moiety for a broad‐spectrum of activity towards cancer cell lines HepG2, MCF‐7, WI‐38, and VERO (Figure 1). [12] While Bhavesh Kumar and his co‐workers highlighted the effect of nucleobase‐based barbiturates on bleomycin‐dependent DNA damage activities, and the results of their study provide the important clues into the molecular mechanisms of DNA damage induced by bleomycin‐iron complex responses to the alteration of barbituric acid and nucleobase hybrid molecules [13] …”

Synthesis, characterization, thermal, anticancer studies, and density functional theory for potentially active pyrimidine‐based complexes

“…10 These pyrimidine-containing species are essential components in nucleic acids, vitamins, coenzymes, and antibiotics. 11,12 They are employed as hypnotics, anticancer, virucide, antibacterial, and antiinflammatory agents. Furthermore, their metal complexes are more biologically active than their parent ligands and used in a variety of disciplines as catalysts, colorants, and corrosion inhibitors.…”

“…Barbituric acid (BA) is a pyrimidine derivative frequently utilized in the synthesis of barbiturate dyes by adding different substituents to the C‐5 atom of the ring, which was previously diazotized to produce colored azodye ligands 10 . These pyrimidine‐containing species are essential components in nucleic acids, vitamins, coenzymes, and antibiotics 11,12 . They are employed as hypnotics, anticancer, virucide, antibacterial, and anti‐inflammatory agents.…”