3rd International Conference on Chemo and BioInformatics, Kragujevac, September 25-26. 2025. (pp. 512-515)
АУТОР(И) / AUTHOR(S): Fatma Sağdıç, Nenad Janković, Oğuzhan Akgün, Emilija N. Milović, Ferda Ari
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DOI: 10.46793/ICCBIKG25.512S
САЖЕТАК / ABSTRACT:
Cancer is one of the most important health problems of today, which ranks second in the list of known deaths. Leukemia remains one of the most important health problems of today, ranking second among known causes of cancer-related death. Although there are treatments that can be effective, new targets and drugs with high selectivity and efficacy are still needed, particularly for non-solid tumors such as leukemia. Many reported antileukemic agents suffer from poor selectivity and bioavailability. Pyrimidines, as fundamental components of DNA and RNA, have attracted significant attention in drug discovery and development. Among the pyrimidine family, Biginelli-derived tetrahydropyrimidines (THPMs) hold particular importance due to their broad pharmacological potential, including anticancer activity. In this study, THPM molecules, and their nanocomposites were synthesized and characterized by NMR, elemental analysis, DSC, TGA, FTIR, MS, and subsequently assessed for their in vitro anticancer activities. The cytotoxic effects were assessed in K-562, THP-1, and MOLT-4 leukemia cell lines using the MTT assay. Results demonstrated that selected THPM derivatives exhibited potent and selective cytotoxicity in distinct leukemia subtypes: compounds 4b, 4e, 4j, and 4k were most active in CML (K-562) cells: 4c, 4e, and 4g in AML (THP-1) cells; and 4b, 4g, 4j, and 4k in ALL (MOLT-4) cells. The observed selectivity is likely driven by phenotypic and genotypic differences among leukemia cell lines, underscoring the therapeutic potential of THPM scaffolds as targeted antileukemic agents. These findings provide a strong basis for further mechanistic studies and preclinical evaluation.
КЉУЧНЕ РЕЧИ / KEYWORDS:
Tetrahydropyrimidines, Anticancer, Selectivity, Nanocomposites, Leukemia
ПРОЈЕКАТ / ACKNOWLEDGEMENT:
This study was supported by the Turkish Scientific and Technological Research Council (TÜBİTAK) 1071 Program and by the Ministry of Education, Science and Technological Development (NITRA) Bilateral Cooperation Program (Project Code: 2559).
ЛИТЕРАТУРА / REFERENCES:
- R. Kaur, P. Kaur, S. Sharma, G. Singha, S. Mehndiratta, P.M.S. Bedia, K. Nepalia, Anti-cancer pyrimidines in diverse scaffolds: a review of patent literature, Recent Patents Anti-Cancer Drug Discovery, 10 (2015) 23-71.
- P. Biginelli, Aldureides of ethylic acetoacetate and ethylic oxaloacetate, Gazzeta Chimica Italiana, 23i (1893) 360- 416.
- L. V. Chopda, P.N. Dave, Recent Advances in Homogeneous and Heterogeneous Catalyst in Biginelli Reaction from 2015-19: A Concise Review, Chemistry Select, 5 (2020) 5552-5572.
- S. Mahgoub, M-K. El-Sayed, M.F. El-Shehry, S.M. Awad, Y.E. Mansour, S.S. Fatahala, Synthesis of Novel Calcium Channel Blockers with ACE2 inhibition and dual antihypertensive /Anti-Inflammatory Effects: Apossible Therapeutic tool for COVID-19, Bioorganic Chemistry, (2021) 105272.
- R. Kaur, S. Chaudhary, K. Kumar, M.K. Gupta, R. K. Rawa, Recent synthetic and medicinal perspectives of dihydropyrimidinones: A review, European Journal of Medicinal Chemostry, 132 (2017) 108-134.
- S. Cesarini, A. Spallarossa, A. Ranise, S. Schenone, C. Rosano, P. La Colla, G. Sanna, B. Busonera, R. Loddo, N-acylated and N,N-diacylated imidazolidine-2-thione derivatives and N,N- diacylated tetrahydropyrimidine-2(1H)-thione analogues: synthesis and antiproliferative activity. European Journal of Medicinal Chemistry, 44(3) (2009) 1106–1118.
- N. E. Uko, O.F. Güner, J.P. Bowen, D.F. Matesic, Akt Pathway Inhibition of the Solenopsin Analog, 2-Dodecylsulfanyl-1,-4,-5,-6-tetrahydropyrimidine, Anticancer Research, 39(10) (2019) 5329–5338.