In order to show antiproliferation and cancerous cell growth inhibition of quinazoline derivatives, a series of 2-(chloromethyl)-3-phenylquinazolin-4(3H)-ones (H1–H11) were synthesized. In vitro cytotoxic activities were evaluated against three human cancer cell lines: A549, MCF-7 and SW1116 using colorimetric MTT assay. Comparing their effects together and with cisplatin as a positive control indicated that H3, H5 and H6 exhibited better antitumor activities on A549 cell line with IC50 values less than 10 μM versus 12 μM for cisplatin. In the case of MCF-7 and SW1116 cell lines, almost all compounds displayed better cytotoxic activities than cisplatin. Molecular docking studies were applied on epidermal growth factor receptor (EGFR) as the main target of quinazoline scaffolds in cancer therapy to predict the binding energies, binding modes and orientation of these ligands toward the active site of the receptor. In silico physicochemical parameters and ADMET profiling calculations also were done. All compounds showed lower binding energies than erlotinib, the inhibitor of EGFR. Taken together, our findings showed potential anticancer effect of quinazoline compounds bearing various phenyl ring substitutions.
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M. Saeedi, M. Mohammadi-Khanaposhtani, P. Pourrabia, N. Razzaghi, R. Ghadimi, S. Imanparast, Bioorg. Chem. 83, 161 (2019)
S. Ravez, O. Castillo-Aguilera, P. Depreux, L. Goossens, Expert Opin. Ther. Pat. 25, 789 (2015)
P.C. Sharma, G. Kaur, R. Pahwa, A. Sharma, H. Rajak, Curr. Med. Chem. 18, 4786 (2011)
K. Rakesh, H. Manukumar, D.C. Gowda, Bioorg. Med. Chem. Lett 25, 1072 (2015)
S. Gatadi, T.V. Lakshmi, S. Nanduri, Eur. J. Med. Chem. 170, 157 (2019)
J. Bartroli, E. Turmo, M. Algueró, E. Boncompte, M.L. Vericat, L. Conte, J. Med. Chem. 41, 1869 (1998)
Z. Wang, M. Wang, X. Yao, Y. Li, J. Tan, L. Wang, Eur. J. Med. Chem. 53, 275 (2012)
A. Hameed, M. Al-Rashida, M. Uroos, S.A. Ali, A.M. Ishtiaq, Expert Opin. Ther. Pat. 28, 281 (2018)
Y. Le, Y. Gan, Y. Fu, J. Liu, W. Li, X. Zou, J. Enzyme. Inhib. Med. 35, 555 (2020)
A.-M. Alaa, L.A. Abou-Zeid, K.E.H. ElTahir, R.R. Ayyad, A.-A. Magda, A.S. El-Azab, Euro. J. Med. Chem. 121, 410 (2016)
J. Fricker, Lancet. Oncol. 7, 621 (2006)
S. Garofalo, R. Rosa, R. Bianco, G, , Tortora. Expert Opin. Ther. Pat. 18, 889 (2008)
G. Marzaro, A. Guiotto, A. Chilin, Expert Opin. Ther. Pat. 22, 223 (2012)
M.N. Noolvi, H.M. Patel, V. Bhardwaj, A. Chauhan, Euro. J. Med. Chem. 46, 2327 (2011)
W. Dohle, F.L. Jourdan, G. Menchon, A.E. Prota, P.A. Foster, P. Mannion, J. Med. Chem. 61, 1031 (2018)
S. El-Sayed, K. Metwally, A.A. El-Shanawani, L.M. Abdel-Aziz, H. Pratsinis, D. Kletsas, Chem. Cent. J. 11, 1 (2017)
F.L. Faraj, M. Zahedifard, M. Paydar, C.Y. Looi, N. Abdul Majid, H.M. Ali, Sci. World J. 2014, 1 (2014)
N. Rahmannejadi, S. Khabnadideh, I. Yavari, Monatsh. Chem. 149, 2085 (2018)
N. Rahmannejadi, I. Yavari, S. Khabnadideh, J. Heterocycl. Chem. 57, 978 (2020)
N. Rahmannejadi, K. Zomorodian, Z. Faghih, Z. Faghih, S. Khabnadideh, J. Pharm. Res. Int. 20, 1 (2017)
Z. Faghih, N. Rahmannejadi, R. Sabet, K. Zomorodian, M. Asad, S. Khabnadideh, Res. Pharm. Sci. 14, 115 (2019)
P. Ramesh, D. Srinivasulu, D. Subbarao, K. Hemakumar, D. Rajasekhar, C. Nagaraju, Der Pharm. Lett. 4, 1344 (2012)
H. Patel, A. Shirkhedkar, S. Bari, K. Patil, A. Arambhi, C. Pardeshi, Bull. Fac. Pharm. 56, 83 (2018)
P. Selvam, N. Murugesh, M. Chandramohan, C. Pannecouque, E.D. Clercq, Indian J. Pharm. Sci. 72, 806 (2010)
H.-Z. Li, H.-Y. He, Y.-Y. Han, X. Gu, L. He, Q.-R. Qi, Molecules 15, 9473 (2010)
Z. Faghih, A. Neshat, P. Mastrorilli, V. Gallo, Z. Faghih, S. Gilanchi, Inorg. Chim. Acta. 512, 119896 (2020)
M. Fereidoonnezhad, H.R. Shahsavari, S. Abedanzadeh, A. Nezafati, A. Khazali, P. Mastrorilli, M. Babaghasabha, J. Webb, Z. Faghih, Z. Faghih, S. Bahemmat, M. Hassan Beyzavi, New J. Chem. 42, 8681 (2018)
W. Humphrey, A. Dalke, K. Schulten, J. Mol. Graph. 14, 33 (1996)
M. Fereidoonnezhad, S.M.H. Tabaei, A. Sakhteman, H. Seradj, Z. Faghih, Z. Faghih, J. Mol. Struct. 1221, 128689 (2020)
M. Fereidoonnezhad, Z. Faghih, A. Mojaddami, Z. Rezaei, A. Sakhteman, Int. J. Pharm. Res. 16, 981 (2017)
R. Sabet, S. Khabnadideh, D. Fathi, L. Emami, J. Pharm. Res. Int. 22, 1 (2019)
L. Emami, L. Zamani, R. Sabet, K. Zomorodian, Z. Rezaei, Z. Faghih, Trends Pharmacol. Sci. 6, 113 (2020)
R.S. Giri, H.M. Thaker, T. Giordano, J. Williams, D. Rogers, K.K. Vasu, Bioorg. Med. Chem. 18, 2796 (2010)
K. Metwally, H. Pratsinis, D. Kletsas, Eur. J. Med. Chem. 133, 340 (2017)
W. Huang, R. Huang, M.S. Attene-Ramos, S. Sakamuru, E.E. Englund, J. Inglese, Bioorg. Med Chem. Lett. 21, 5239 (2011)
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Emami, L., Faghih, Z., Khabnadideh, S. et al. 2-(Chloromethyl)-3-phenylquinazolin-4(3H)-ones as potent anticancer agents; cytotoxicity, molecular docking and in silico studies. J IRAN CHEM SOC (2021). https://doi.org/10.1007/s13738-021-02168-1
- Molecular docking