One-pot Synthesis, Cytotoxic Evaluation and Molecular Docking of 3,4,7,8-tetrahydroquinazoline-2,5-(1H,6H)-dione Derivatives Synthesis, cytotoxic evaluation and molecular docking of tetrahydroquinazolinones
International Pharmacy Acta,
Vol. 5 No. 1 (2022),
19 June 2022
Page e5: 1-9
In this study, a proper multicomponent process was developed for synthesis of tetrahydroquinazolinone derivatives. Dimedone, urea, and various aryl aldehydes were applied to the evaluation of a one-pot reaction under solvent-free and solvent conditions in the presence of CaCl2.2H2O and aniline as catalysts. It was optimized by employing at 110 °C and 10% mol for CaCl2.2H2O and 60% mol in the presence of EtOH at room temperature for aniline. All chemical structures of tetrahydroquinazolinones were determined by FT-IR, 1HNMR, 13CNMR, mass spectroscopy, elemental analysis, and melting point. The synthesized compounds were evaluated for their cytotoxicity activity against MCF-7 cell line by MTT assay. All of the synthesized compounds showed moderate cytotoxicity activity against MCF-7 cell line. Especially, Compound 4h was the most potent compound. Also, the potential EGFR inhibitory activity of these compounds was investigated in silico using molecular docking simulation method. Especially compound 4h which showed the lowest ΔGbind results (-7.37 Kcal/mol).
- One-pot synthesis
- Molecular docking
How to Cite
Alafeefy AA, Kadi AA, Al-Deeb OA, El-Tahir KEH, Al-jaber NA. Synthesis, analgesic and anti-inflammatory evaluation of some novel quinazoline derivatives. Eur J Med Chem. 2010; 45:4947-4952.
Rathod SV, Shinde KW, Kharkar PS, Shah CP. Synthesis, Molecular Docking and Biological Evaluation of New Quinoline Analogues as Potent Anti-breast Cancer and Antibacterial Agents. Iran. J. Pharm. Sci. 2020; 16(4):17-30.
Abdalgane HA, Mohammed HH, Askar FW. Synthesis and biological evaluation studies of Some quinazolinone derivatives as antimicrobial and antioxidant agents. J Pharm Sci & Res. 2019; 11: 54-57.
Hussein MA. Synthesis, anti-inflammatory, and structure antioxidant activity relationship of novel 4-quinazoline. Med Chem Res. 2013; 22: 4641-4653.
Gilbert IH. Inhibitors of dihydrofolate reductase in Leishmania and trypanosomes. Biochim Biophys Acta. 2002; 1587:249-257.
Jackman AL, Taylor GA, Gibson W, Kimbell R, Brown M, Calvert AH, et al. A quinazoline antifolate thymidylate synthase inhibitor that is a potent inhibitor of L1210 tumor cell growth in vitro and in vivo: a new agent for clinical study. Cancer Res. 1991; 51: 5579-5586.
Ismail RS, Ismail NS, Abuserii S, El Ella DAA. Recent advances in 4-aminoquinazoline based scaffold derivatives targeting EGFR kinases as anticancer agents. Future J Pharm Sci. 2016; 2: 9-19.
Xu H, Yu Y, Marciniak D, Rishi AK, Sarkar FH, Kucuk O, et al. Epidermal growth factor receptor (EGFR)-related protein inhibits multiple members of the EGFR family in colon and breast cancer cells. Mol Cancer Ther. 2005; 4:435-342.
Zayed MF, Rateb HS, Ahmed S, Khaled OA, Ibrahim SRM. Quinazolinone-Amino Acid Hybrids as Dual Inhibitors of EGFR Kinase and Tubulin Polymerization. Molecules. 2018; 23: 1699.
Jiang N, Zhai X, Zhao Y, Liu Y, Qi B, Tao H, et al. Synthesis and biological evaluation of novel 2-(2-arylmethylene) hydrazinyl-4-aminoquinazoline derivatives as potent antitumor agents. Eur J Med Chem. 2012; 54: 534-541.
El-Azab AS, Al-Dhfyan A, Abdel-Aziz AAM, Abou-Zeid LA, Alkahtani HM, Al-Obaid AM, et al. Synthesis, anticancer and apoptosis-inducing activities of quinazoline–isatin conjugates: epidermal growth factor receptor-tyrosine kinase assay and molecular docking studies. J Enzyme Inhib Med Chem. 2017; 32: 935-944.
Nasab RR, Hassanzadeh F, Khodarahmi GA, Mirzaei M, Rostami M, Jahanian-Najaf abadi A. Synthesis, characterization, cytotoxic screening, and density functional theory studies of new derivatives of quinazolin-4(3H)-one Schiff bases. Res Pharm Sci. 2017; 12:444-455.
Vibhute S, Jamale D, Undare S, Valekar N, Kolekar G, Anbhule P. An efficient, one-pot three components synthesis of [1,2,4] triazoloquinazolinone derivatives using anthranilic acid as green catalyst. Res Chem Intermed. 2017; 43: 4561 .
Hassankhani A, Mosaddegh E. An efficient synthesis oftetrahydrotetrazolo[1,5a]quinazoline derivatives by a three-component reaction of 5-aminotetrazole, arylaldehydes, and dimedone. Scientia Iranica. C. 2015; 22: 942-947.
Karami B, Eskandari Kh, Ansari G. A Practical Approach to the Effective Synthesis of 1,8-Dioxoöctahydroxanthene Derivatives By The Use of ICl3/SiO2 and In(CF3SO3)3 As Recyclable and Highly Efficient Catalysts. Der Chemica Sinica. 2017; 8: 342- 354.
Sahu PK, Sahu PK, Gupta SK, Agarwal DD. Chitosan: An Efficient, Reusable, and Biodegradable Catalyst for Green Synthesis of Heterocycles. Ind. Eng. Chem. Res. 2014; 53: 2085-2091.
Janati F, Heravi MM, Mirshokraie A. Superparamagnetic Iron Oxide as an Efficient Catalyst for the One-Pot, Solvent-Free Synthesis of 5,5-Disubstituted Hexahydropyrimidines and Their Spiro Analogues. J Chem. 2012; 2013: 1-5.
Heravi MM, Ranjbar L, Derikvand F, Alimadadi B, Oskooie HA, Bamoharram FF. A three component one-pot procedure for the synthesis of [1,2,4]triazolo/benzimidazolo-quinazolinone derivatives in the presence of H6P2W18O62 · 18H2O as a green and reusable catalyst. Mol Divers. 2008; 12:181-185.
Hassankhani A. Multicomponent reaction for the synthesis of 2,3- dihydroquinazolin-4(1H)-ones using isatoic anhydride, aldehydes and NH4OAc catalyzed by SnCl2.2H2O under solventfree conditions. Eurasian Chem. Commun. 2019; 1: 248-256.
Nasab RR, Karami B, Khodabakhshi S. Selective Solvent‐Free Biginelli Condensation using Tungstate Sulfuric Acid as Powerful and Reusable Catalyst. Bull Chem React Eng Catal. 2014; 9: 149.
Nasab RR, Mansourian M, Hassanzadeh F, Shahlaei M. Exploring the interaction between epidermal growth factor receptor tyrosine kinase and some of the synthesized inhibitors using combination of in-silico and in-vitro cytotoxicity methods. Res Pharm Sci. 2018; 13:509-522 .
Kumar KS, Ganguly S, Veerasamy R, De Clercq E. Synthesis, antiviral activity and cytotoxicity evaluation of Schiff bases of some 2-phenyl quinazoline-4 (3) H-ones. Eur J Med Chem. 2010;45: 5474-5479.
Mukhopadhyay C, Rana S, Butcher R J. FeCl3 catalysed two consecutive aminomethylation at β carbonyl compounds: an easy access to hexahydropyrimidines and its spiro analogues. Tetrahedron Lett. 2011; 52: 4153–4157.
Armstrong RW, Combs A P, Tempest P A, Brown S D, Keating T A. Multiple-component condensationstrategies for combinatorial library synthesis. A C S. 1996; 29: 123–131.
Domling A, Ugi I. Multicomponent reactions with isocyanides. Angew Chem. 2000; 39: 3168–3210.
Jafari E, Khajouei MR, Hassanzadeh F, Hakimelahi GH, Khodarahmi GA. Quinazolinone and quinazoline derivatives: recent structures with potent antimicrobial and cytotoxic activities. Res Pharm Sci. 2016;11:1-14.
Hosseinzadeh L, Aliabadi A, Rahnama M, Sadeghi HMM, Khajouei MR. Synthesis and cytotoxic evaluation of some new 3-(2-(2-phenylthiazol-4-yl) ethyl)-quinazolin-4 (3H) one derivatives with potential anticancer effects. Res Pharm Sci. 2017;12:290-298.
Nasab RR, Hassanzadeh F, Khodarahmi GA, Rostami M, Mirzaei M, Jahanian-Najafabadi A, et al. Docking study, synthesis and antimicrobial evaluation of some novel 4-anilinoquinazoline derivatives. Res Pharm Sci. 2017;12(5):425-433.
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