Synthesis, characterization, cytotoxic screening, and density functional theory studies of new derivatives of quinazolin-4(3H)-one Schiff bases

Rezvan Rezaee Nasab, Farshid Hassanzadeh, Ghadam Ali Khodarahmi, Mahmoud Mirzaei, Mahboubeh Rostami, Ali Jahanian-Najaf abadi


A series of novel derivatives of quinazolinone Schiff bases were synthesized from benzoic acid starting material and evaluated for potential cytotoxic activities against the human breast adenocarcinoma (MCF-7) and the human colon adenocarcinoma (HT-29) cell lines. Compared to the reference drug, these compounds showed good cytotoxic activities against studied cell lines especially compounds 4d and 4e. The ground-state geometries of these compounds (4a-g) were optimized at the B3LYP/6–31G* density functional theory (DFT) level. Then maximum absorptions electron affinity, ionization potential, electronegativity (χ), energy gap (Egap), hardness (η), softness (S), electrophilicity (ω), and electrophilicity index (ωi) were calculated and discussed. The quantitative structure-activity relationship (QSAR) properties including the physicochemical parameters were also evaluated and studied. The computed properties of our novel synthesized compounds were compared with erlotinib compound.


Quinazolinone; Schiff base; Density functional theory; Cytotoxic activity; Quantitative structure-activity relationship

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Khodarahmi Gh, Jafari E, Hakimelahi Gh, Abedi D, Rahmani Khajouei M, Hassanzadeh F. Synthesis of some new quinazolinone derivatives and evaluation of their antimicrobial activities. Iran J Pharm Res. 2012;11(3):789-797.

Farag AA, Khalifa EM, Sadik NA, Abbas SY, Al-Sehemi AG, Ammar YA. Synthesis, characterization, and evaluation of some novel 4 (3H)-quinazolinone derivatives as anti-inflammatory and analgesic agents. Med Chem Res. 2013;22(1):440-452.

Zhu S, Wang J, Chandrashekar G, Smith E, Liu X, Zhang Y. Synthesis and evaluation of 4-quinazolinone compounds as potential antimalarial agents. Eur J Med Chem. 2010;45(9):3864-3869.

Alagarsamy V, Pathak US. Synthesis and antihypertensive activity of novel 3-benzyl-2-substituted-3H-[1, 2, 4] triazolo [5, 1-b] quinazolin-9-ones. Bioorg Med Chem. 2007;15(10):3457-3462.

Hosseinzadeh L, Aliabadi A, Kalantari M, Mostafavi A, Rahmani Khajouei M. Synthesis and cytotoxicity evaluation of some new 6-nitro derivatives of thiazole-containing 4-(3H)-quinazolinone. Res Pharm Sci.2016;11(3):210-218.

Shiva Prasad K, Shiva Kumar L, Chandan S, Vijaya B, Revanasiddappa HD. Synthesis, characterization and DNA interaction studies of copper (II) complex of 4 (3H)-quinazolinone-derived Schiff base. Anal Univ Bucuresti Chimie. 2011;20(1):7-13.

Kumar A, Sharma P, Kumari P, Lal Kalal B. Exploration of antimicrobial and antioxidant potential of newly synthesized 2, 3-disubstituted quinazoline-4 (3H)-ones. Bioorg Med Chem Lett. 2011;21(14):4353-4357.

Kosaka T, Yamaki E, Mogi A, Kuwano H. Mechanisms of resistance to EGFR TKIs and development of a new generation of drugs in non-small-cell lung cancer. J BioMed Biotechnol. 2011;2011:165214.

Barbosa ML, Lima LM, Tesch R, Sant'Anna CM, Totzke F, Kubbutat MH, et al. Novel 2-chloro-4-anilino-quinazoline derivatives as EGFR and VEGFR-2 dual inhibitors. Eur J Med Chem. 2014;71:1-14.

Emregül KC, Düzgün E, Atakol O. The application of some polydentate Schiff base compounds containing aminic nitrogens as corrosion inhibitors for mild steel in acidic media. Corros Sci. 2006;48(10):3243-3260.

Cozzi PG. Metal–Salen Schiff base complexes in catalysis: practical aspects. Chem Soc Rev. 2004;33(7):410-421.

Fakhari AR, Khorrami AR, Naeimi H. Synthesis and analytical application of a novel tetradentate N(2)O(2) Schiff base as a chromogenic reagent for determination of nickel in some natural food samples. Talanta. 2005;66(4):813-817.

Zhang J, Cheng P, Ma Y, Liu J, Miao Z, Ren D, et al. An efficient nano CuO-catalyzed synthesis and biological evaluation of quinazolinone Schiff base derivatives and bis-2, 3-dihydroquinazolin-4 (1H)-ones as potent antibacterial agents against Streptococcus lactis. Tetrahedron Lett. 2016;57(47):5271-5277.

Irfan A, Muhammad S, Al-Sehemi AG, Al-Assiri MS, Kalam A. Structure modification to tune the electronic and charge transport properties of solar cell materials: quantum chemical study. Int J Electrochem Sci. 2015;10:3600-3612.

Liu J, Herbert JM. Local excitation approximations to time-dependent density functional theory for excitation energies in solution. J Chem Theory Comput. 2016;12(1):157-166.

Al-Sehemi AG, Irfan A, Asiri AM, Ammar YA. Synthesis, characterization and density functional theory study of low cost hydrazone sensitizers. Bull Chem Soc Ethiop. 2015;29(1):137-148.

Kohn W, Becke AD, Parr RG. Density functional theory of electronic structure. J Phys Chem. 1996;100(31):12974-12980.

Parr RG, Szentpaly Lv, Liu S. Electrophilicity index. J Am Chem Soc. 1999;121(9):1922-1924.

Al-Sehemi AG, Irfan A, Alrumman SA, Hesham A. Antibacterial activities, DFT and QSAR studies of quinazolinone compounds. Bull Chem Soc Ethiop. 2016;30(2):307-316.

Nanda AK, Ganguli S, Chakraborty R. Antibacterial activity of some 3-(arylideneamino)-2-phenyl-quinazoline-4 (3H)-ones: synthesis and preliminary QSAR studies. Molecules. 2007;12(10):2413-2426.

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(11):5474-5479.

Chaudhry AR, Ahmed R, Irfan A, Shaari A, Al-Sehemi AG. Quantum chemical approach toward the electronic, photophysical and charge transfer properties of the materials used in organic field-effect transistors. Mater Chem Phys. 2013;138(2-3):468-478.

Krishnakumar V, Muthunatesan S. DFT studies of the structure and vibrational assignments of 4-hydroxy quinazoline and 2-hydroxy benzimidazole. Spectrochim Acta A Mol Biomol Spectrosc. 2007;66(4-5):1082-1090.

Politzer P, Murray JS. Relationships of electrostatic potentials to intrinsic molecular properties. Comp Theor Chem. 1996;3:649-660.

Smits RA, Adami M, Istyastono EP, Zuiderveld OP, van Dam CM, de Kanter FJ, et al. Synthesis and QSAR of quinazoline sulfonamides as highly potent human histamine H4 receptor inverse agonists. J Med Chem. 2010;53(6):2390-2400.

Karabulut S, Sizochenko N, Orhan A, Leszczynski J. A DFT-based QSAR study on inhibition of human dihydrofolate reductase. J Mol Graph Model. 2016;70:23-29.

Xi Z, Yu Z, Niu C, Ban S, Yang G. Development of a general quantum‐chemical descriptor for steric effects: density functional theory based QSAR study of herbicidal sulfonylurea analogues. J Comput Chem. 2006;27(13):1571-1576.

Lipinski CA. Lead-and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol. 2004;1(4):337-341.

Khodarahmi Gh, Jafari E, Hakimelahi Gh, Abedi D, Rahmani Khajouei M, Hassanzadeh F. Synthesis of Some new quinazolinone derivatives and evaluation of their antimicrobial activities. Iran J Pharm Res. 2012;11(3):789-797.

Krishnan SK, Ganguly S, Veerasamy R, Jan B. Synthesis, antiviral and cytotoxic investigation of 2-phenyl-3-substituted quinazolin-4 (3H)-ones. Eur Rev Med Pharmacol Sci. 2011;15(6):673-681.

Raghavendra NM, Thampi PP, Gurubasavarajaswamy PM. Synthesis and antimicrobial activity of some novel substituted piperazinyl-quinazolin-3 (4H)-ones. J Chem. 2008;5(1):23-33.

Zahedifard M, Faraj FL, Paydar M, Yeng Looi C, Hajrezaei M, Hasanpourghadi M, et al. Synthesis, characterization and apoptotic activity of quinazolinone Schiff base derivatives toward MCF-7 cells via intrinsic and extrinsic apoptosis pathways. Sci Rep. 2015;5:11544.

Rezaee Nasab R, Karami B, Khodabakhshi S. Selective solvent-free biginelli condensation using Tungestat Sulfuric Acid as powerful and reusable catalyst. Bul Chem React Engin Cat, 2014;9(2): 148-154.


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