Synthesis and Study of the Effect New Pyrazoles and Oxadiazole Linked to the 1,4-Dihydropyridine Ring on Breast Cancer

Journal of Chemical Health Risks

دوره 13، شماره 4، اسفند 2023، صفحه 701-719   

نوع مقاله: Original Article

شناسه دیجیتال (DOI): 10.22034/jchr.2023.1996251.1817

نویسندگان

Adiba Saaduldeen Ali؛ Tahseen Saddam Fandi Al-Mathkuri^*

Department of Chemistry, College of Science, University of Misan, Misan, 62001, Iraq

چکیده

The Hantzsch reaction created a new series comprising 1,4-dihydropyridine pyrazoles and oxa diazoles (DHP) by initially synthesizing DHP esters, then its carbohydrates, and subsequent treatment with hydrazine. Pyrazole derivatives (Am₁ and Am₂) were obtained via the reaction of hydrazines with acetylacetone or ethyl acetoacetate, whereas the oxadiazole derivative (Am₃) was prepared via reaction with carbon disulfide in an alkaline medium. The prepared compounds were identified using spectroscopic techniques (FTIR, ¹H and ¹³C NMR, and mass spectrometry). The anti-breast cancer activity of new compounds was evaluated. This cytotoxicity activity afforded that compound (AS) was the strongest in this group together with an IC₅₀ = 100.24µg mL^-1, whereas compound (AT) demonstrated the lowest potency, with an IC₅₀ value of 300 µg mL^-1. The Hantzsch reaction was used in the synthesis of a new 1,4-dihydropyridine that has pyrazole and oxadiazole moieties. The activity of in vitro cytotoxicity (MTT cell viability assay) was determined. In vitro MCF7 cells were used in the evaluation of the cytotoxicity activity (MTT cell viability assay) of new compounds. This cytotoxicity activity meant that compound (AS) was the strongest in this group, with an IC₅₀ of 100.24 µg mL^-1, while compound (AT) had the least potency, with an IC₅₀ value of 300 µg mL^-1. Based on our findings, we can infer that 1,4-dihydropyridine derivatives (DHPs) are noteworthy heterocyclic compounds with pharmacological potential.  This cytotoxicity activity meant that compound (AS) was the strongest in this group, with an IC₅₀ of 100.24 µg mL^-1, while compound (AT) had the least potency, with an IC₅₀ value of 300 µg mL^-1. 

کلیدواژه‌ها

Hantzsch reaction؛ Hydrazine؛ Derivatives؛ MTT؛ Anti breast cancer

مراجع

1. 1. Nasr-Esfahani M., Rafiee Z., Kashi H., 2016. Nanoparticles tungstophosphoric acid supported on polyamic acid: catalytic synthesis of 1, 8-dioxo-decahydroacridines and bulky bis (1, 8-dioxo-decahydroacridine) s. Journal of the Iranian Chemical Society. 13,1449-1461.
2. Khodja I.A., Ghalem W., Dehimat Z.I., Boulcina R., Carboni B., Debache A., 2014. Solvent-Free Synthesis of Dihydropyridines and Acridinediones via a Salicylic Acid–Catalyzed Hantzsch Multicomponent Reaction. Synthetic Communications. 44(7), 959-967.
3. Ibrahim N.S., Mohamed M.F., Elwahy A.H., Abdelhamid I.A., 2018. Biological activities and docking studies on novel Bis 1, 4-DHPS linked to arene core via ether or ester linkage. Letters in Drug Design & Discovery. 15(10), 1036-1045.
4. Olejníková P., ŠVORC Ľ., Olšovská D., Panáková A., Vihonská Z., Kovaryová K., Marchalín Š., 2014. Antimicrobial activity of novel C2-substituted 1, 4-dihydropyridine analogues. Scientia pharmaceutica. 82(2), 221-232.
5. Vijesh A.M., Isloor A.M., Peethambar S.K., Shivananda K.N., Arulmoli T., Isloor N.A., 2011. Hantzsch reaction: synthesis and characterization of some new 1, 4-dihydropyridine derivatives as potent antimicrobial and antioxidant agents. European Journal of Medicinal Chemistry. 46(11), 5591-5597.
6. Fan X., Li Y., Zhang X., Qu G., Wang J., 2007. An efficient and green preparation of 9‐arylacridine‐1, 8‐dione derivatives. Heteroatom Chemistry: An International Journal of Main Group Elements. 18(7),786-790.
7. Bade T.S., Ebrahimi H.P., Alsalim T.A., Titinchi S.J., Abbo H.S., Bolandnazar Z., Ebrahimi A., 2017. A novel series of 1, 4-Dihydropyridine (DHP) derivatives bearing thiazolidin-4-one: From synthesis to structure. Journal of Molecular Structure. 1138,136-148.
8. Al-Wahaibi L.H., Mohamed A.A., Tawfik S.S., Hassan H.M. and El-Emam A.A., 2021. 1, 3, 4-Oxadiazole N-Mannich bases: synthesis, antimicrobial, and anti-proliferative activities. Molecules. 26(8), 2110.
9. Kumar B.P., Rao A.T., Prasad V.S.R., Shree A.J., 2016. Synthesis of novel 1, 3, 4-oxadiazole analogues with expected antibacterial activity. International Journal of Chemical Sciences. 14, 1877-1885.
10. Sharma M., Singhvi I., Ali Z.M., Kumar M., Dev S.K., 2018. Synthesis and biological evaluation of natural cyclic peptide. Future Journal of Pharmaceutical Sciences. 4(2), 220-228.
11. Chandrakantha B., Shetty P., Nambiyar V., Isloor N., Isloor A.M., 2010. Synthesis, characterization and biological activity of some new 1, 3, 4-oxadiazole bearing 2-flouro-4-methoxy phenyl moiety. European Journal of Medicinal Chemistry. 45(3), 1206-1210.
12. Sattar A., Abbasi M.A., Siddiqi S.Z., Nafeesa K., Ahmad I., 2016. Synthesis and antibacterial study of some s-substituted aliphatic analogues of 2-mercapto-5-(1-(4-toluenesulfonyl) piperidin-4-yl)-1, 3, 4-oxadiazole. Tropical Journal of Pharmaceutical Research. 15(6), 1267-1274.
13. Küçükgüzel Ş.G., Oruç E.E., Rollas S., Şahin F., Özbek A., 2002. Synthesis, characterisation and biological activity of novel 4-thiazolidinones, 1, 3, 4-oxadiazoles and some related compounds. European Journal of Medicinal Chemistry. 37(3),197-206.
14. Maslat A.O., Abussaud M., Tashtoush H., Al-Talib M., 2002. Synthesis, antibacterial, antifungal and genotoxic activity of bis-1, 3, 4-oxadiazole derivatives. Polish Journal of Pharmacology. 54(1),55-60.
15. Khalilullah H., J Ahsan M., Hedaitullah M., Khan S., Ahmed B., 2012. 1, 3, 4-oxadiazole: a biologically active scaffold. Mini Reviews in Medicinal Chemistry. 12(8), 789-801.
16. Poudyal B., Bharghav G., 2021. A review of pyrazole an its derivative. National Journal of Pharmaceutical Sciences. 1(1), 34-41.
17. Azzam R.A., Elsayed R.E., Elgemeie G.H., 2020. Design, synthesis, and antimicrobial evaluation of a new series of N-sulfonamide 2-pyridones as dual inhibitors of DHPS and DHFR enzymes. ACS omega.  5(18), 10401-10414.
18. Çetin G., Cetin B., Colak B., Asan M., Demirel G., Cansaran Duman D.E.M.E.T., Akcelik N., Şimsek R., 2022. A new perspective for biological activities of novel hexahydroquinoline derivatives. Journal of Research in Pharmacy. 26(1), 219-230.
19. Murthy Y.L.N., Rajack A., Ramji M.T., Praveen C., Lakshmi K.A., 2012. Design, solvent free synthesis, and antimicrobial evaluation of 1, 4 dihydropyridines. Bioorganic & Medicinal Chemistry Letters. 22(18), 6016-6023.
20. Sanchez L.M., Sathicq Á.G., Jios J.L., Baronetti G.T., Thomas H.J., Romanelli G.P., 2011. Solvent-free synthesis of functionalized pyridine derivatives using Wells-Dawson heteropolyacid as catalyst. Tetrahedron Letters. 52(34), 4412-4416.
21. Zhang Y., Wu C., Zhang N., Fan R., Ye Y., Xu J., 2023. Recent Advances in the Development of Pyrazole Derivatives as Anticancer Agents. International Journal of Molecular Sciences. 24(16), 12724.
22. Kagne R.P., Nikam G.H., Kalalawe V.G., Niwadange S.N., Munde D.R., 2017. An efficient protocol for synthesis of 1, 4-dihydropyridine derivatives by using graphene oxide nano particles as a catalyst. Journal of Chemistry and Chemical Science. 7, 1064.
23. Bazargan L., Fouladdel S., Shafiee A., Amini M., Ghaffari S.M., Azizi E., 2008. Evaluation of anticancer effects of newly synthesized dihydropyridine derivatives in comparison to verapamil and doxorubicin on T47D parental and resistant cell lines in vitro. Cell Biology and Toxicology. 24, 165-174.
24. Movassagh B., Rooh H., Bijanzadeh H.R., 2013. A mild and highly efficient one-pot synthesis of 1, 3, 5-triaryl-2-pyrazolines. Chemistry of Heterocyclic Compounds. 48(11),1719-1721.
25. Ko S., Yao C.F., 2006. Ceric ammonium nitrate (CAN) catalyzes the one-pot synthesis of polyhydroquinoline via the Hantzsch reaction. Tetrahedron. 62(31), 7293-7299.
26. Linciano P., Benedetti R., Pinzi L., Russo F., Chianese U., Sorbi C., Altucci L., Rastelli G., Brasili L., Franchini S., 2021. Investigation of the effect of different linker chemotypes on the inhibition of histone deacetylases (HDACs). Bioorganic Chemistry. 106, 104462.
27. Pattao S.R., Rabara P.A., Pattan J.S., Bukitagar A.A., Wakalc V., Musmade D., 2009. Synthesis and evaluation of some novel substituted 1, 3, 4-oxadiazole and pyrazole derivatives for antitubercular activity. Indian Journal of Chemistry. Sect. B: Organic chemistry, including medical chemistry. 48(10), 1453-1456.
28. Tomma J.H., Hussein D.F., Jamel N.M., 2016. Synthesis and Characterization of Some New Quinoline-2-one, Schiff bases, Pyrazole and Pyrazoline Compounds Derived From Hydrazide Containing Isoxazoline or Pyrimidine Cycles. Iraqi Journal of Science. 1316-1332.
29. Mayekar A.N., Yathirajan H.S., Narayana B., Sarojini B.K., Kumari N.S., 2010. Synthesis and antimicrobial studies on new substituted 1, 3, 4-oxadiazole derivatives bearing 6-bromonaphthalene moiety. International Journal of Chemistry. 2(1), 38.
30. Ulloora S., Shabaraya R., Ranganathan R., Adhikari A.V., 2013. Synthesis, anticonvulsant and anti-inflammatory studies of new 1, 4-dihydropyridin-4-yl-phenoxyacetohydrazones. European Journal of Medicinal Chemistry. 70, 341-349.
31. Gowda J., Khadar A., Kalluraya B., Kumari N.S., 2010. Microwave assisted synthesis of 1, 3, 4-oxadiazoles carrying benzimidazole moiety and their antimicrobial properties. Indian Journal of Chemistry. Sect. B: Organic chemistry, including medical chemistry. 49(8), 1130-1134.

32 .Mulugeta E., Samuel Y., 2022. Synthesis of benzimidazole-sulfonyl derivatives and their biological activities. Biochemistry Research International. https://doi.org/10.1155/2022/7255299.

33. Alam M.J., Alam O., Naim M.J., Nawaz F., Manaithiya A., Imran M., Thabet H.K., Alshehri S., Ghoneim M.M., Alam P., Shakeel F., 2022. Recent advancement in drug design and discovery of pyrazole biomolecules as cancer and inflammation therapeutics. Molecules. 27(24), 8708.
34. Sophy M.A., Abdel Reheim M.A.M., 2020. Synthesis of Some New 1, 3, 4-Oxadiazole, Pyrazole, and Pyrimidine Bearing Thienopyrazole Moieties. Current Organic Synthesis. 17(8), 661-670.