Facile synthesis and anticancer activity of novel dihydropyrimidinone derivatives

• Autorzy: Bhat Mashooq A. , Al-Omar Mohamed A. , Naglah Ahmed M. , Al-Dhfyan Abdullah

Identyfikatory

DOI

10.2478/pjct-2022-0004

• Języki publikacji: EN

Abstrakty

EN

The enaminone, (2E)-3-(dimethylamino)-1-(3,4,5-trimethoxyphenyl) prop-2-en-1-one was prepared by refluxing 3,4,5-trimethoxy acetophenone with dimethylformamide dimethylacetal (DMF–DMA) without solvent for 12 h. The dihydropyrimidinone derivatives (1–9) were prepared by reacting enaminone, substituted benzaldehydes and urea in glacial acetic acid. The compounds (1–9) were synthesized in significant yield using one step multicomponent reaction. Structures of all the novel synthesized compounds were characterized and confirmed by various spectroscopic methods. The compounds were evaluated for their anti-cancer activity against HepG2 cancer cell line. Compound 9 displayed significant anti-cancer activity. During the apoptotic assay, it showed a significant increase in necrosis from 1.97% to 12.18% as compared to the control. Mechanism of anti-proliferation was performed by cell cycle distribution assay, which showed a decrease in G2+M from 12.90 to 8.13 as compared to control.

Słowa kluczowe

EN

Dihydropyrimidinone; enaminone; 3,4,5-trimethoxybenzoyl moiety

• Wydawca: West Pomeranian University of Technology. Publishing House
• Czasopismo: Polish Journal of Chemical Technology
• Rocznik: 2022
• Tom: Vol. 24, nr 1
• Strony: 23--28
• Opis fizyczny: Bibliogr. 25 poz., rys., wz.

Twórcy

autor

Bhat Mashooq A.

• Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

autor

Al-Omar Mohamed A.

• Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

autor

Naglah Ahmed M.

• Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

autor

Al-Dhfyan Abdullah

• Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

Bibliografia

• 1. Folkers, K., Harwood, H.J. & Johnson, T.B. (1932). Researches on pyrimidines. cxxx. synthesis of 2-keto-1,2,3,4-tetrahydropyrimidines. J. Am. Chem. Soc. 54, 3751. DOI: 10.1021/ja01348a040.
• 2. Atwal, K.S., Ahmed, S.Z., Bird, J.E., Delaney, C.L., Dickinson, K.E., Ferrara, F.N., Hedberg, A., Miller, A.V., Moreland, S. & O’Reilly, B.C. (1992). Dihydropyrimidine angiotensin II receptor antagonists. J. Med. Chem. 35, 4751−4763. DOI: 10.1021/jm00103a014.
• 3. Rana, K., Kaur, B. & Kumar, B. (2004). Synthesis and antihypertensive activity of some dihydropyrimidines. Indian J. Chem. 43, 1553−1557.
• 4. Rovnyak, G.C., Kimball, S.D., Beyer, B., Cucinotta, G., DiMarco, J.D., Gougoutas, J., Hedberg, A., Malley, M., Mc-Carthy, J.P., Zhang, R. & Moreland, S. (1995). Calcium entry blockers and activators: conformational and structural determinants of dihydropyrimidine calcium channel modulators. J. Med. Chem. 38, 119–29. DOI: 10.1021/jm00001a017.
• 5. Atwal, K.S., Swanson, B.N., Unger, S.E., Floyd, D.M., Moreland, S., Hedberg, A. & Reilly, B.C.O. (1991). Dihydropyrimidine calcium channel blockers. 3. 3-Carbamoyl-4-aryl-1,2,3,4-tetrahydro-6-methyl-5-pyrimidinecarboxylic acid esters as orally effective antihypertensive agents. J. Med. Chem. 34, 806−811. DOI: 10.1021/jm00106a048.
• 6. Kappe, C.O. (1993). 100 years of the Biginelli dihydropyrimidine synthesis. Tetrahedron, 49, 6937−6963. DOI: 10.1016/S0040-4020(01)87971-0.
• 7. Beena, K.P., Suresh, R., Rajasekaran, A. & Manna, P.K. (2016). Dihydropyrimidinones- a versatile Scaffold with diverse biological activity. J. Pharm. Sci. & Res. 8, 741−746.
• 8. Jalali, M., Mahdavi, M., Memarian, H.R., Ranjbar, M., Soleymani, M., Fassihi, A. & Abedi, D. (2012). Antimicrobial evaluation of some novel derivatives of 3,4-dihydropyrimidine-2(1H)-One. Res. Pharm. Sci. 7, 243–247. PMID: 23248675.
• 9. Pramanik, T., Pathan, A.H., Gupta, R., Singh, J. & Singh, S. (2015). Dihydropyrimidinone derivatives: green synthesis and effect of electronic factor on their antimicrobial properties. Res. J. Pharm. Biol. Chem. Sci. 6, 1152–1157.
• 10. Shaikh, A. & Meshram, J.S. (2015). Design, synthesis and pharmacological assay of novel azo derivatives of dihydropyrimidinones. Cogent Chem. 1, 1019809. DOI:10.1080/23 312009.2015.1019809.
• 11. Liu, Y., Liu, J., Zhang, R., Guo, Y., Wang, H., Meng, Q., Sun, Y. & Liu, Z. (2019). Synthesis, characterization, and anticancer activities evaluation of compounds derived from 3,4-dihydropyrimidin-2(1H)-One. Molecules, 24, 891. DOI: 10.3390/molecules24050891.
• 12. Abdel-Latif, N.A., Sabry, N.M., Mohamed, A.M. & Abdulla, M.M. (2007). Synthesis, analgesic, and antiparkinsonian profiles of some pyridine, pyrazoline, and thiopyrimidine derivatives. Monatshefte fur Chemie., 138, 715–724. DOI: 10.1007/s00706-007-0656-8.
• 13. Bairagi, K.M., Younis, N.S., Emeka, P.M., Sangtani, E., Gonnade, R.G., Venugopala, K.N., Alwassil, O.I., Khalil, H.E. & Nayak, S.K. (2020). Antidiabetic activity of dihydropyrimidine scaffolds and structural insight by single crystal x-ray studies. Med. Chem. 16, 996–1003. DOI: 10.2174/15734064166661912 27123048.
• 14. Farghaly, A.M., AboulWafa, O.M., Elshaier, Y.A.M., Badawi, W.A., Haridy, H.H. & Mubarak, H.A.E. (2019). Design, synthesis, and antihypertensive activity of new pyrimidine derivatives endowing new pharmacophores. Med. Chem. Res. 28, 360–379. DOI: 10.1007/s00044-019-02289-6.
• 15. Silva, G.C.O., Correa, J.R., Rodrigues, M.O., Alvim, H.G.O., Guido, B.C., Gatto, C.C., Wanderley, K.A., Fioramonte, M., Gozzo, F.C., De Souza, R.O.M.A. & Neto, B.A.D. (2015). The Biginelli reaction under batch and continuous flow conditions: catalysis, mechanism and antitumoral activity. RSC Adv. 5, 48506–48515. DOI: 10.1039/c5ra07677c.
• 16. Soumyanarayanan, U., Bhat, V.G., Kar, S.S. & Mathew J.A. (2012). Monastrol mimic Biginelli dihydropyrimidinone derivatives: synthesis, cytotoxicity screening against HepG2 and HeLa cell lines and molecular modeling study. Org. Med. Chem. Lett., 2, 23. DOI: 10.1186/2191-2858-2-23.
• 17. Romagnoli, R., Baraldi, P.G., Cara, C.L., Hamel, E., Basso, G., Bortolozzi, R. & Viola, G. (2010). Synthesis and biological evaluation of 2-(3’,4’,5’-trimethoxybenzoyl)-3-aryl/arylaminobenzo[b]thiophene derivatives as a novel class of antiproliferative agents. Eur. J. Med. Chem. 45, 5781–5791. DOI: 10.1016/j.ejmech.2010.09.038.
• 18. Tseng, H.H., Chuah, Q.Y., Yang, P.M., Chen, C.T., Chao, J.C., Lin, M.D. & Chiu, S.J. (2012). Securin enhances the anti-cancer effects of 6-methoxy-3-(3’,4’,5’-trimethoxy-benzoyl)-1H-indole (BPR0L075) in human colorectal cancer cells. PLoS One, 7, e36006. DOI: 10.1371/journal.pone.0036006.
• 19. Bhat, M.A., Al-Omar, M.A., Ghabbour, H. & Naglah, A. (2018). A one-pot Biginelli synthesis and sharacterization of novel dihydropyrimidinone derivatives containing piperazine/morpholine moiety. Molecules, 23, 1559. DOI: 10.3390/molecules23071559.
• 20. Bhat, M. A., Al-Omar, M. A., Naglah., A. & Al-Dhfyan, A. (2020). Biginelli synthesis of novel dihydropyrimidinone derivatives containing phthalimide moiety. J. Chem. 2020, 1−10. DOI: 10.1155/2020/4284628.
• 21. Bhat, M.A., Al-Omar, M.A., Naglah, A. & Khan, A.A. (2019). Enaminone-derived pyrazoles with antimicrobial activity. J. Chem. 2019, 1−10. DOI: 10.1155/2019/2467970.
• 22. Bhat, M.A., Al-Omar, M.A., Khan, A.A., Alanazi, A.M. & Naglah, A.M. (2019). Synthesis and antihepatotoxic activity of dihydropyrimidinone derivatives linked with 1, 4-benzodioxane. Drug Des. Devel. Ther. 13, 2393. DOI 10.2147/DDDT.S198865.
• 23. Bhat, M.A., Al-Omar, M.A. & Naglah, A. (2018). Synthesis and in vivo anti-ulcer evaluation of some novel piperidine linked dihydropyrimidinone derivatives. J. Enzyme. Inhib. Med. Chem. 33, 978−988. DOI: 10.1080/14756366.2018.1474212.
• 24. Bhat, M.A., Ahmed, A.F., Wen, Z.H., Al-Omar, M.A. & Abdel-Aziz, H.A. (2017). Synthesis, anti-inflammatory and neuroprotective activity of pyrazole and pyrazolo[3,4-d] pyridazine bearing 3,4,5-trimethoxyphenyl. Med. Chem. Res. 26, 1557−1566. DOI: 10.1007/s00044-017-1870-5.
• 25. Bhat, M.A., Al-Omar, M.A., Naglah, A., Kalmouch, A. & Al-Dhfyan, A. (2019). Synthesis and characterization of novel Biginelli dihydropyrimidinone derivatives containing imidazole moiety. J. Chem. 2019, 1−10. DOI:10.1155/2019/3131879.

Uwagi

Opracowanie rekordu ze środków MEiN, umowa nr SONP/SP/546092/2022 w ramach programu "Społeczna odpowiedzialność nauki" - moduł: Popularyzacja nauki i promocja sportu (2022-2023).