Synthesis and Biological 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 160–180°C for 2 h gave the intermediate 7 in high yield. This intermediate was then reacted with amines in acetic acid at 180°C 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, cytotoxic, cancer
Article Details
References
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[3] Mellinghoff I. K.; Sawyers C. L. The emergence of resistance to targeted cancer therapy. Pharmacogenomics., 3 (2002), 603–623.
[4] Welsch ME, Snyder SA, Stockwell BR. Privileged scaffolds for library design and drug discovery. Curr Opin Chem Biol., 14 (2010), 1–15.
[5] Asif M. Various chemical and biological activities of pyridazinone derivatives. Cent Eur J Exp Biol., 5 (2017), 1–19.
[6] Nikaljea AP, Bahetia K. Computer based drug design of various heterocyclic compounds having anticancer activity: a brief review. J Bioinform Genom Proteom., 2 (2017), 1–13.
[7] Yadav MR, Naik PP, Gandhi HP, Chauhan BS, Giridhar R. Design and synthesis of 6,7-dimethoxyquinazolinone analogs as multi-targeted ligands for α1- and α11-receptors antagonism. Bioorg Med Chem Lett., 23 (2013), 3959–3966.
[8] (a) Sheta, A. & Wijdan, I.A. Synthesis and characterization of new quinazoline-4(3H)-one Schiff bases. J Chem Pharm Res., 5 (2013), 42–45; (b) Amer M. Alanazi, Alaa A.-M. Abdel-Aziz, Ibrahim A. Al-Suwaidan, Sami G. Abdel-Hamide, Taghreed Z. Shawar, Adel S. El-Azab. Design, synthesis and biological evaluation of some novel substituted quinazolines as antitumor agents. Eur. J. Med. Chem., 79 (2014), 446–454; (c) Malleshappa N. Noolvi, Harun M. Patel. Synthesis, method optimization, anticancer activity of 2,3,7-trisubstituted Quinazolinone derivatives and targeting EGFR-tyrosine kinase by rational approach. 1st Cancer Update. Arab. J. Chem., 6 (2013), 35–48; (d) H. Fleita, R. M. Mohareb, O. K. Sakka. Antitumor and antileishmanial evaluation of novel heterocycles derived from quinazolinone scaffold: a molecular modeling approach. Med. Chem. Res., 22 (2013), 2207–2221.
[9] Zaranappa et al. Synthesis and Antioxidant Activity of 3-Substituted Schiff bases of Quinazoline-2,4-diones. Int J Chem Tech Res., 4 (2012), 1527–1533.
[10] Krishnan, S.K. et al. Synthesis, antiviral and cytotoxic investigation of 2-phenyl-3-substituted Quinazolin-4(3H)-ones. Eur Rev Med Pharm Sci., 15 (2011), 673–681.
[11] Patel, N.B. et al. Synthesis and microbial studies of (4-oxo-thiazolidinyl) sulfonamides bearing quinazolin-4(3H)-ones. Acta Pol Pharm Drug Res., 67 (2010), 267–275.
[12] Saravanan, G., Pannerselvam, P. & Prakash, C.R. 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] Abid, O.H. & Ahmed, A.H. 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] Pati, B. & Banerjee, S. Quinazolines: an illustrated review. J Adv Pharm Edu Res., 3 (2013), 136–151.
[15] Katrin, S.N. Chemotherapy and Dietary Phytochemical Agents. Chem ther Res Pract., 3 (2012), 22–27.
[16] Manasa, A.K., Sidhaye, R.V., Radhika, G. & Nalini, C.N. Synthesis, antioxidant and anticancer activity of quinazoline derivatives. Current Pharma Research., 1 (2011), 101–105.
[17] Nerkar, B., Saxena, A., Ghone, S. & Thakeri, A.K. 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] Danilov, A.V. Targeted therapy in chronic lymphocytic leukemia: past, present, and future. Clin Ther., 35 (2013), 1258–1270.
[19] Ahmed, M.F. & Youns, M. 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.
[20] Kumar, D. Design, synthesis, and cytotoxic evaluation of novel imidazolone fused quinazolinone derivatives. Arabian J. Chem. doi:10.1016/j.arabjc.2014.07.001 (2014).
[21] Faraj, F.L. et al. Synthesis, Characterization, and Anticancer Activity of New Quinazoline Derivatives against MCF-7 Cells. Sci Wld J. doi:10.1155/2014/212096 (2014).
[22] Ahmed, K., El Bharathi, M., Ramaiah, D., Dastagiri, J.S., Reddy, A., Viswanath, A., FarehenSultana, S., N. C.V.L., Pushpavalli, ManikaPal-Bhadra, Hemant, K.S., N. Sastry, Aarti, J., Subrata, Sen, Surekha, Zingde. Quinazolinone linked pyrrolo
[23] Scudiero, D.A., Shoemaker, R.H., Paull, K.D., Monks, A., Tierney, S., Nofziger, T.H., Currens, M.J., Seniff, D., Boyd, M. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res., 48 (1988), 4827–4833.