Synthesis and DNA Photocleavage Activity of S-Alkylated 2-thiopyrimidines Current Trends in Biotechnology and Chemical Research (original) (raw)
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Objective: 1-(subsituted)-4,4,6-trimethyl-3,4-dihydropyrimidine-2(1H)-thione: Green synthesis, antibacterial activity and DNA photocleavage activity. Methods: In the present study, 1-(subsituted)-4,4,6-trimethyl-3,4-dihydropyrimidine-2(1H)-thione has been achieved under mild reaction conditions by employing microwave assisted and grind stone method. All the synthesized compounds were evaluated for their DNA nicking activity. Some of them were selected as to evaluate their antibacterial effect against gram-positive (Enterococcus) and gram-negative (Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa) bacteria. The outcome of the study indicating that compounds containing flour, methoxy and chloro substituent were found to exhibit complete DNA cleavage at 40 μg/μl concentration. Results: The reported compounds synthesized through greener methods such as grindstone and microwave assisted synthesis. Conclusion: Some of the compounds have exhibited promising antibacterial and DNA Photoclevage activity.
UVA photoactivation of DNA containing halogenated thiopyrimidines induces cytotoxic DNA lesions
Journal of photochemistry and photobiology. B, Biology, 2015
Photochemotherapy, the combination of a photosensitiser and ultraviolet (UV) or visible light, is an effective treatment for skin conditions including cancer. The high mutagenicity and non-selectivity of photochemotherapy regimes warrants the development of alternative approaches. We demonstrate that the thiopyrimidine nucleosides 5-bromo-4-thiodeoxyuridine (SBrdU) and 5-iodo-4-thiodeoxyuridine (SIdU) are incorporated into the DNA of cultured human and mouse cells where they synergistically sensitise killing by low doses of UVA radiation. The DNA halothiopyrimidine/UVA combinations induce DNA interstrand crosslinks, DNA-protein crosslinks, DNA strand breaks, nucleobase damage and lesions that resemble UV-induced pyrimidine(6-4)pyrimidone photoproducts. These are potentially lethal DNA lesions and cells defective in their repair are hypersensitive to killing by SBrdU/UVA and SIdU/UVA. DNA SIdU and SBrdU generate lethal DNA photodamage by partially distinct mechanisms that reflect the...
Synthesis and Biological Evaluation of Novel Thio-1,4-dihydropyrimidine-5-carboxylate Derivatives
Asian Journal of Chemistry, 2013
INTRODUCTION Heterocycles are ubiquitous to among pharmaceutical compounds 1. Pyrimidine moiety is an important class of N-containing heterocycles widely used as key building blocks for pharmaceutical agents. These compounds exhibit a wide spectrum of pharmacophore, as they act as bactericidal, fungicidal 2-5 , analgesic 6 , antioxidant 7 , antihypertensive 8 , antifilarial 9 and antitumor agents 10. Preclinical data from literature indicates the continuing research in polysubstituted pyrimidine as potential antitumor agents 11-13. Among these, thiouracils in particular are used as antiinflammatory and virucidal agents 14. The biological and synthetic significance places this scaffold at a prestigious position in medicinal chemistry research. The key role pyrimidines play in cellular processes has made them valuable leads for drug discovery. One important class of pyrimidines is 2-thiopyrimidine (2-TP) and its derivatives, which are also recognized as 2-mercaptopyrimidine compounds 15. In 2-thiopyrimidine ring, sulfur atom serves as an interesting replacement for the existing oxygen atom bonded to C-2 in uridine base 16,17. Based on this approach, 2-thiopyrimidines have attracted significant attention of synthetic chemists and biochemists 18-20. Pathak et al. 21 have reported potential activity of 2-thiopyrimidine derivatives against Mycobacterium tuberculosis (Mtb). One-step synthesis of 3,4-dihydropyrimidin-2(1H)-one by three-component condensation of aldehydes, ethyl acetoacetate
Chemical & Pharmaceutical Bulletin, 2013
A variety of novel thieno[3,2-d]pyrimidines with different decorating functional groups were synthesized as a part of a study aiming to enrich the arsenal of chemotherapeutic agents for the treatment of cancer. The design of synthetic molecules based on DNA-interchelating properties by hydrogen bond formation. The reported compounds herein are: 4-aminothienopyrimidine derivatives 4a, b and their 4-substituted phenylamino analogues 8a, b; 4-thienopyrimidin-4-ones 5a, b; N-alkyl thienopyrimidin-4-ones 6a-g; 4-chlorothienopyrimidines 7a, b and thienopyrimidoquinazolinones 9a, b which are the structural mimics of 8a, b. The synthesized molecules were evaluated for their in vitro cytotoxic activity against human breast cancer cell line (MCF-7). Biological screening revealed varying cytotoxic potencies of the tested molecules compared with Doxorubicin as a reference drug. The cytotoxicity results from the study suggested that the synthesized molecules are potential antitumor agents and compound 4a was the most potent with an IC 50 2.04 nm.
2021
All-organic, heavy-atom-free photosensitizers based on thionation of nucleobases are receiving increased attention because they are easy to make, noncytotoxic, work both in the presence and absence of molecular oxygen and can be readily incorporated into DNA and RNA. In this contribution, the DNA and RNA fluorescent probe, thieno[3,4-d]pyrimidin-4(1H)-one, has been thionated to develop thieno[3,4-d]pyrimidin-4(1H)-thione, which is nonfluorescent and absorbs near-visible radiation with about 60% higher efficiency. Steady-state absorption and emission spectra are combined with transient absorption spectroscopy and CASPT2 calculations to delineate the electronic relaxation mechanisms of both pyrimidine derivatives in aqueous and acetonitrile solutions and to explain the origin of the remarkable fluorescence quenching in the thionated compound. It is demonstrated that thieno[3,4-d]pyrimidin-4(1H)-thione efficiently populates the long-lived and reactive triplet state in hundreds of femto...
DNA-binding studies of a series of novel water-soluble derivatives of 1,4-dihydropyridine
Biopolymers and Cell
Aim. To the determine DNA interaction modes for a series of 1,4-dihydropyridines with different biological activities synthesized in the Latvian Institute of Organic Synthesis. Methods. Affinity of the compounds to DNA was detected by UV/VIS spectrometry and re-proofed by means of spectrofluorimetry, EBr extrusion assay, cyclic voltammetry and DNA melting. Radical scavenging was tested by electron paramagnetic resonance spectroscopy, peroxynitrite binding was monitored spectrophotometrically, protection of DNA against hydroxyl radical was determined by gel electrophoresis. Results. In a series of water-soluble monocyclic derivatives of 1,4-dihydropyridine with carboxylate groups in position-4 the different affinity to DNA was determined mainly by substituents in positions 3 and 5. 1,4-DHP with ethoxycarbonyl groups in positions 3 and 5 (AV-153) manifested high affinity to DNA. Strong effects were observed in the spectra of tricyclic fused derivatives (PP-150-Na and PP-544-NH 4). Unlike AV-153, J-4-96 did not extrude EtBr from the complex with DNA, this indicates binding to minor groove. Ability of PP-544-NH 4 to intercalate DNA molecule was proved electrochemically and by DNA melting. No correlation between affinity of a 1,4-DHP to DNA and capabilities of the compound to bind peroxynitrite, to scavenge hydroxyl radical or to protect DNA against the above radical were observed. Conclusions. DNA-binding activities of 1,4-DHP are evidently determined by groups in positions 3 and 5. Tricyclic fused 1,4-DHP derivatives are also good DNA binders. Ability to interact with DNA does not correlate with other effects produced by the compounds. K e y w o r d s: 1,4-dihydropyridines, DNA binding, peroxynitrite binding, hydroxyl radical scavenging, DNA protection.