Synthesis and In vitro Cytotocxic Evaluation of New Quinazolinone Derivatives
Main Article Content
Abstract
The paper presents a simple and efficient synthesis of a series of new quinazolinone derivatives 8a-h. First, the reaction of 5-hydroxyanthranilic acid (6) with acetic anhydride at 160–180oC for 2 h gave the intermediate 7 in high yield. This intermediate was then reacted with amines in acetic acid at 180 oC for 14 h afforded new quinazolinone derivatives 8a-h in 77–92%. Synthesized compounds were structurally confirmed using spectroscopic methods: 1H, 13CNMR and mass spectrum. The bioassay result using three cancer cell lines including SKLU-1 (lung cancer), MCF-7 (breast cancer) and HepG-2 (liver cancer) showed that only compound 8h exhibited significant cytotoxic effect against cancer cell lines tested with IC50 values of 23.09, 27.75 and 30.19 µg/ mL, respectively.
Keywords:
Quinazolinone, cytotoxicity, cancer, base, in vitro, derivative.
References
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[5] M. Asif, Various chemical and biological activities of pyridazinone derivatives, Cent Eur J Exp Biol (5) (2017) 1–19.
[6] A.P. Asif, K. Bahetia, Computer based drug design of various heterocyclic compounds having anticancer activity: a brief review, J Bioinform Genom Proteom (2) (2017) 1–13.
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[8] (a). A. Shetha & I. A. Wijdan, Synthesis and characterization of new quinazoline–4(3H)-one Schiff bases, J Chem Pharm Res (5) (2013) 42–45; (b). A. M. Alanazi, A.-M. Alaa, Abdel-Aziz, I. A. Al-Suwaidan, S. G. Abdel-Hamide, T. Z. Shawer, A. S. El-Azab, Design, synthesis and biological evaluation of some novel substituted quinazolines as antitumor agents, Eur. J. Med. Chem (79) (2014) 446-454. https://doi.org/10. 1016/j.ejmech.2014.04.029; (c) M. N. Noolvi, H. M. Patel, Synthesis, method optimization, anticancer activity of 2,3,7-trisubstituted Quinazoline derivatives and targeting EGFR-tyrosine kinase by rational approach: 1st Cancer Update, Arab. J. Chem (6) (2013)35-48. https:// doi.org/10.1016/j.arabjc.2010.12.031; (d). D. H. Fleita, R. M. Mohareb, O. K. Sakka, Antitumor and antileishmanial evaluation of novel heterocycles derived from quinazoline scaffold: a molecular modeling approach, Med. Chem. Res (22) (2013) 2207-2221. https://doi.org/10.1007/ s00044-012-0213-9.
[9] H.M. Vagdevi, M.R. Lokesh, B.C. Gowdarshivannanavar, Synthesis and Antioxidant Activity of 3-Substituted Schiff bases of Quinazoline-2,4-diones, Int J Chem Tech Res (4) (2012) 1527–1533.
[10] S.K. Krishnan, S. Ganguly, R. Veerasamy, B. Ran, Synthesis, antiviral and cytotoxic investigation of 2-phenyl-3-substituted quinazolin -4(3H)-ones, Eur Rev Med Pharm Sci (15) (2011) 673–681.
[11] N.B. Patel, V.N. Patel, H.R. Patel, F.M. Shaikh, J. C. Patel, Synthesis and microbial studies of (4-oxo-thiazolidinyl) sulfonamides bearing quinazolin-4(3h) ones, Acta Polo Pharm Drug Res (67) (2010) 267–275.
[12] G. Saravanan, P. Pannerselvam, C.R. Prakash, Synthesis, analgesic and anti-inflammatory screening of novel Schiff bases of 3-amino-2-methyl quinazolin 4-(3H)-one, Der Pharmacia Lett (2) (2010) 216–226.
[13] O.H. Abid & A.H. Ahmed, Synthesis and characterization of novel quinazoline derivatives via reaction of isatoic anhydride with schiff’s base, Inter J Appl Nat Sci (2) (2013) 11–20.
[14] B. Pati & S. Banerjee, Quinazolines: an illustrated review, JAdv Pharm Edu Res (3) (2013) 136–151.
[15] S.N. Katrin, Chemotherapy and Dietary Phytochemical Agents, Chem ther Res Prac (3) (2012) 22–27. doi:10.1155/2012/282570.
[16] A.K. Manasa, R.V. Sidhaye, G. Radhika, C.N. Nalini, Synthesis, antioxidant and anticancer activity of quinazoline derivatives, Current Pharma Research (1) (2011) 101–105.
[17] B. Nerkar, A. Saxena, S. Ghone, A.K. Thakeri, In Silico Screening, Synthesis and In Vitro Evaluation of Some Quinazolinone and Pyridine Derivatives as Dihydrofolate Reductase Inhibitors for Anticancer Activity, E-Journal of Chem (6) (2009) 97–102.
[18] A.V. Danilov, Targeted therapy in chronic lymphocytic leukemia: past, present, and future, Clin Ther (35) (2013) 1258–1270. https://doi.org/ 10.1016/j.clinthera.2013.08.004.
[19] M.F. Ahmed, M. Youns, Synthesis and Biological Evaluation of a Novel Series of 6, 8‐Dibromo‐4 (3H) quinazolinone Derivatives as Anticancer Agents, Archiv der Pharmazie (346) (2013) 610–617. https://doi.org/10.1002/ardp.201300158.
[20] D. Kumar, Design, synthesis and cytotoxic evaluation of novel imidazolone fused quinazolinone derivatives, Arabian J. Chem. https://10.1016/j.arabjc.2014.07.001 (2014).
[21] F.L. Faraj, M. Zahedifard, Synthesis, Characterization, and Anticancer Activity of New Quinazoline Derivatives against MCF-7 Cells, Sci. Wld J. 212096; https://doi.rog/10.1155/2014/ 212096 (2014).
[22] A. Kamal, E.V. Bharathi, M.J Ramaiah, D. Dastagiri, J. S. Reddy, A.Viswanath, F. Sultana, S.N.C.V.L. Pushpavalli, M.P. Bhadra, H.K. Srivastava, G. N. Sastry.; Aarti J.; Subrata Sen.; Surekha Zingde, Quinazolinone linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates: Design, synthesis and biological evaluation as potential anticancer agents, Bioorg. Med. Chem 18 (2), (2010) 526-542. https://doi. org/10.1016/j.bmc.2009.12.015.
[23] D.A. Scudiero, R.H. Shoemaker, K.D. Paull, A. Monks, S. Tierney, T.H. Nofziger, M.J. Currens, D. Seniff, M. Boyd, Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay, Cancer Res (48) (1988) 4827–4833.