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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Anticancer Evaluation of Novel Quinazolinone Acetamides: Synthesis and Characterization

Author(s): Farhana Hakim, Roshan Salfi*, Darna Bhikshapathi and Abdullah Khan

Volume 22, Issue 5, 2022

Published on: 04 January, 2022

Page: [926 - 932] Pages: 7

DOI: 10.2174/1871520621666210524164351

Price: $65


Background: According to the global cancer report 2019, the burden of cancer will exceed more than 18 million, becoming one of the major causes of global mortality rate. There is a pressing need to establish novel drug candidates for cancer treatment, though many anticancer agents are available in the market owing to their adverse effects. In recent years, quinazoline and its derivatives have been considered as a novel class of cancer chemotherapeutic agents that show promising activity against different tumors.

Objective: To evaluate the anti-cancer potential of the novel class of quinazoline tethered acetamide derivatives against six different cancer cell lines.

Methods: A novel series of various substituted quinazolinone acetamides were synthesized through a feasible scheme. The synthetic scheme involves the conversion of benzoxazinone (from anthranilic acid and benzoyl chloride) intermediate to 3-amino quinazoline-4-one which further converted to the final amide by tethering with the propionyl chloride employing Schotten-Baumann Reaction conditions. All the synthesized derivatives characterized by IR, 1HNMR and MASS spectral methods and anti-cancer activity were evaluated by employing MTT assay for six cancer cell lines and one normal human cell line.

Results: All the synthesized compounds were screened for anti-cancer activity against six cancer cell lines, including A 549 (lung), DU 145 (prostate), HT 29 (colon), MCF-7 (breast), SiHA (cervical), B16F10 (mouse skin melanoma) and one normal human fibroblast cell lines. All the compounds displayed a decent cytotoxicity profile when compared with the standard drug doxorubicin. Among the synthesized compounds (5a to 5n) tested, two compounds, 5f and 5g have demonstrated excellent cytotoxicity against SiHA and MCF-7 cancer cell lines.

Conclusion: Comparatively most of the compounds displayed decent cytotoxicity potential relative to the standard drug doxorubicin. Further investigations are needed to establish the detailed mechanism of action of the developed novel quinazolinone acetamides.

Keywords: Quinazolinone, anti-cancer activity, EGRF-TK, Schotten-Baumann reaction, MTT assay, cell line.

Graphical Abstract
Global cancer report-2018, International Agency for Research on Cancer. WHO report, 2018.
Alafeefy, A.M.; Ceruso, M.; Al-Tamimi, A.M.S.; Del Prete, S.; Capasso, C.; Supuran, C.T. Quinazoline-sulfonamides with potent inhibitory activity against the α-carbonic anhydrase from Vibrio cholerae. Bioorg. Med. Chem., 2014, 22(19), 5133-5140.
[] [PMID: 25194929]
Alafeefy, A.M.; Ceruso, M.; Al-Jaber, N.A.; Parkkila, S.; Vermelho, A.B.; Supuran, C.T. A new class of quinazoline-sulfonamides acting as efficient inhibitors against the α-carbonic anhydrase from Trypanosoma cruzi. J. Enzyme Inhib. Med. Chem., 2015, 30(4), 581-585.
[] [PMID: 25373503]
De Martino, J.K.; Boger, D.L. Glycinamide ribonucleotide transformylase (GAR TFase) as a target for cancer therapy. Drug Fut, 2008, 33, 969-979.
Curran, W.J. New chemotherapeutic agents: Update of major chemoradiation trials in solid tumors. Oncology, 2002, 63(Suppl. 2), 29-38.
[] [PMID: 12466642]
Nurgali, K.; Jagoe, R.T.; Abalo, R. Editorial: Adverse effects of cancer chemotherapy: Anything new to improve tolerance and reduce sequelae? Front. Pharmacol., 2018, 9, 245-247.
[] [PMID: 29623040]
El-Messery, S.M.; Hassan, G.S.; Nagi, M.N.; Habib, E.E.; Al-Rashood, S.T.; El-Subbagh, H.I. Synthesis, biological evaluation and molecular modeling study of some new methoxylated 2-benzylthio-quinazoline-4(3H)-ones as nonclassical antifolates. Bioorg. Med. Chem. Lett., 2016, 26(19), 4815-4823.
[] [PMID: 27554444]
Arteaga, C.L.; Johnson, D.H. Tyrosine kinase inhibitors-ZD1839 (Iressa). Curr. Opin. Oncol., 2001, 13(6), 491-498.
[] [PMID: 11673690]
Barker, A.J.; Gibson, K.H.; Grundy, W.; Godfrey, A.A.; Barlow, J.J.; Healy, M.P.; Woodburn, J.R.; Ashton, S.E.; Curry, B.J.; Scarlett, L.; Henthorn, L.; Richards, L. Studies leading to the identification of ZD1839 (IRESSA): An orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer. Bioorg. Med. Chem. Lett., 2001, 11(14), 1911-1914.
[] [PMID: 11459659]
Barker, AJ Johnstone, C Preparation of 4-anilino-7- heteroarylquinazolines as tyrosine kinase inhibitors. WO 97/30044 A1, 1997.
El-Azab, A.S.; Al-Omar, M.A.; Abdel-Aziz, A.A.M.; Abdel-Aziz, N.I.; el-Sayed, M.A.A.; Aleisa, A.M.; Sayed-Ahmed, M.M.; Abdel-Hamide, S.G. Design, synthesis and biological evaluation of novel quinazoline derivatives as potential antitumor agents: Molecular docking study. Eur. J. Med. Chem., 2010, 45(9), 4188-4198.
[] [PMID: 20599299]
Tiwari, S.K.; Sachan, S.; Mishra, A.; Tiwari, S.; Pandey, V. The anti-cancer activity of some novel 4-anilino quinazoline derivatives as tyrosine kinase (EGFR) inhibitor and the quantitative structure activity relationships. Int J Pharm Life Sci., 2015, 6, 4819-4828.
Al-Suwaidan, I.A.; Abdel-Aziz, A.A.M.; Shawer, T.Z.; Ayyad, R.R.; Alanazi, A.M.; El-Morsy, A.M.; Mohamed, M.A.; Abdel-Aziz, N.I.; El-Sayed, M.A.A.; El-Azab, A.S. Synthesis, antitumor activity and molecular docking study of some novel 3-benzyl-4(3H)quinazolinone analogues. J. Enzyme Inhib. Med. Chem., 2016, 31(1), 78-89.
[] [PMID: 25815668]
Saravanan, G.; Alagarsamy, V.; Prakash, C.R.J. Synthesis, characterization and in vitro antimicrobial activity of some 1-(substitutedbenzylidene)-4-(4-(2-(methyl/phenyl)-4-oxoquinazolin-3(4H)-yl) phenyl) semicarbazide derivatives. Saudi Chem Soc., 2015, 19, 3-11.
Alagarsamy, V.; Salomon, V.R.; Vanikavitha, G.; Paluchamy, V.; Chandran, M.R.; Sujin, A.A.; Thangathiruppathy, A.; Amuthalakshmi, S.; Revathi, R. Synthesis, analgesic, anti-inflammatory and antibacterial activities of some novel 2-phenyl-3-substituted quinazolin-4(3H) ones. Biol. Pharm. Bull., 2002, 25(11), 1432-1435.
[] [PMID: 12419954]
Yen, Y.H.; Chu, Y.H. Synthesis of tetrahydro-β-carboline diketopiperazines in [PF6] ionic liquid accelerated by controlled microwave heating. Tetrahedron Lett., 2004, 45, 8137-8140.
Jain, S.; Mishra, P. Synthesis and biological activity of novel N-cycloalkyl-(cycloalkylaryl)-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetamides. Indian J. Heterocycl. Chem., 2004, 13, 307-312.
Carmichael, J.; DeGraff, W.G.; Gazdar, A.F.; Minna, J.D.; Mitchell, J.B. Evaluation of a tetrazolium-based semiautomated colorimetric assay: Assessment of chemosensitivity testing. Cancer Res., 1987, 47(4), 936-942.
[PMID: 3802100]

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