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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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Research Article

Design, Synthesis, Antimicrobial and Anti-biofilm Evaluation, and Molecular Docking of Newly Substituted Fluoroquinazolinones

Author(s): Mohamed F. Zayed, Sabrin R.M. Ibrahim*, EL-Sayed E. Habib, Memy H. Hassan, Sahar Ahmed and Heba S. Rateb

Volume 15, Issue 6, 2019

Page: [659 - 675] Pages: 17

DOI: 10.2174/1573406414666181109092944

Price: $65

Abstract

Background: Quinazolines and quinazolinones derivatives are well known for their important range of therapeutic activities.

Objective: The study aims to carry out the synthesis of some derivatives of substituted fluoroquinazolinones based on structure-based design and evaluation of their antibacterial, antifungal, and anti-biofilm activities.

Methods: Compounds were chemically synthesized by conventional methods. Structures were established on the basis of spectral and elemental analyses. The antimicrobial potential was tested against various microorganisms using the agar disc-diffusion method. MIC and MBC as well as anti-biofilm activity for the highly active compounds were assessed. Moreover, the computational studies were performed using Auto dock free software package (version 4.0) to explain the predicted mode of binding.

Results: All derivatives (5-8), (10a-g), and (A-H) were biologically tested and showed significant antimicrobial activity comparable to the reference compounds. Compounds 10b, 10c, and 10d had a good MIC and MBC against Gram-positive bacteria, whereas 10b and 10d showed significant MIC and MBC against Gram-negative bacteria. However, compounds E and F exhibited good MIC and MBC against fungi. Compound 10c and 8 exhibited significant anti-biofilm activity towards S. aureus and M. luteus. Molecular docking study revealed a strong binding of these derivatives with their receptor-site and detected their predicted mode of binding.

Conclusion: The synthesized derivatives showed promising antibacterial, antifungal, and antibiofilm activities. Modeling study explained their binding mode and showed strong binding affinity with their receptor-site. The highly active compounds 5 and 10c could be subjected to future optimization and investigation to be effective antimicrobial agents.

Keywords: Design, synthesis, fluoroquinazolinone, antibacterial, antifungal, anti-biofilm, molecular docking.

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[1]
Zayed, M.F.; Ahmed, H.E.A.; Omar, A.M.; Abdelrahim, A.S.; El-Adl, K. Design, synthesis and biological evaluation studies of novel quinazolinone derivatives as anticonvulsant agents. Med. Chem. Res., 2013, 22, 5823-5831.
[2]
Connolly, J.D.; Cusack, D.; Sullivan, P.T.; O’Sullivan, T.P.; Guiry, P.J. Synthesis of quinazolinones and quinazolines. Tetrahedron, 2005, 61, 10153-10202.
[3]
Pathak, S.R.; Malhotra, V.; Nath, V.R.; Shanker, K. Synthesis and antihypertensive activity of novel quinazolin-4(3H)-one derivatives. Cent. Nerv. Syst. Agents Med. Chem., 2014, 14, 34-38.
[4]
Zayed, M.F.; Hassan, M.H. Synthesis and biological evaluation studies of novel quinazolinone derivatives as antibacterial and anti-inflammatory agents. Saudi Pharm. J., 2014, 22, 157-162.
[5]
El-Sharief, M.A.; Ahmed, Z.M.; El-Sharief, M.S. Synthesis, characterization, and derivatization of some novel types of fluorinated mono- and bis-imidazolidineiminothiones with antitumor, antiviral, antibacterial, and antifungal activities. J. Fluor. Chem., 2011, 132, 596-611.
[6]
Kumar, K.S.; Ganguly, S.; Veerasamy, R.; Erik, D.C. Synthesis, antiviral activity and cytotoxicity evaluation of Schiff bases of some 2-phenyl quinazoline-4(3)H-ones. Eur. J. Med. Chem., 2010, 45, 5474-5479.
[7]
Abbas, S.E.; Awadallah, F.M.; Ibrahin, N.A.; Said, E.G.; Kamel, G.M. New quinazolinone–pyrimidine hybrids: Synthesis, anti-inflammatory, and ulcerogenicity studies. Eur. J. Med. Chem., 2012, 53, 141-149.
[8]
Ali, Z.; Akhtar, M.J.; Haider, M.R. Design and synthesis of quinazoline-3,4-(4H)-diamine endowed with thiazoline moiety as new class for DPP-4 and DPPH inhibitor. Bioorg. Chem., 2017, 71, 181-191.
[9]
Ram, V.R.; Farhanullah, B.K.; Srivastava, A.K. Synthesis and antihyperglycemic activity of suitably functionalized 3H-quinazolin- 4-ones. Bioorg. Med. Chem., 2003, 1, 2439-2444.
[10]
Aly, M.M.; Mohamed, Y.A.; El-Bayouki, K.A.; Basyouni, W.M.; Abbas, S.Y. Synthesis of some new 4(3H)-quinazolinone-2-carbo-xaldehyde thiosemicarbazones and their metal complexes and a study on their anticonvulsant, analgesic, cytotoxic and antimicrobial activities. Eur. J. Med. Chem., 2010, 45, 3365-3373.
[11]
Al-Rashood, S.T.; Aboldahab, I.A.; Nagi, M.N.; Abouzeid, L.A.; Abdel-Aziz, A.A.; Abdel-Hamide, S.G.; Youssef, K.M.; Al-Obaid, A.M.; El-Subbagh, H.I. Synthesis, dihydrofolate reductase inhibition, antitumor testing, and molecular modeling study of some new 4(3H)-quinazolinone analogs. Bioorg. Med. Chem., 2006, 14, 8608-8621.
[12]
Zayed, M.F.; Hassan, M.H. Design, synthesis and biological evaluation studies of novel quinazoline derivatives as cytotoxic agents. Drug Res., 2013, 63, 210-215.
[13]
Al-Obaid, A.M.; Abdel-Hamide, S.G.; El-Kashef, H.A.; Abdel-Aziz, A.A.; El-Azab, A.S.; Al-Khamees, H.A.; El-Subbagh, H.I. Substituted quinazolines, part 3. Synthesis, in vitro antitumor activity and molecular modeling study of certain 2-thieno-4(3H)-quinazolinone analogs. Eur. J. Med. Chem., 2009, 44, 2379-2391.
[14]
Zayed, M.F.; Ahmed, H.E.A.; Ihmaid, S.; Omar, A.M.; Abdelrahim, A.S. Synthesis and screening of some new fluorinated quinazolinone-sulphonamide hybrids as anticancer agents. J. Taibah. Univ. Med. Sci, 2015, 10, 333-339.
[15]
Ahmed, H.E.A.; Ihmaid, S.K.; Omar, A.M.; Shehata, A.M.; Rateb, H.S.; Zayed, M.F.; Ahmed, S.; Elaasser, M.M. Design, synthesis, molecular docking of new lipophilic acetamide derivatives affording potential anticancer and antimicrobial agents. Bioorg. Chem., 2018, 76, 332-342.
[16]
Ihmaid, S.K.; Ahmed, H.E.A.; Zayed, M.F. The design and development of potent small molecules as anticancer agents targeting EGFR TK and tubulin polymerization. Int. J. Mol. Sci., 2018, 19, 1-15.
[17]
Wakeling, A.E.; Guy, S.P.; Woodburn, J.R.; Ashton, S.E.; Curry, B.J.; Barker, A.J.; Gibson, K.H. An orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res., 2002, 62, 5749-5754.
[18]
Layeva, A.A.; Nosova, E.V.; Lipunova, G.N.; Trashakhova, T.V.; Charushin, V.N. A new approach to fluorinated 4(3H)-quinazolinones. J. Fluor. Chem., 2007, 128, 748-754.
[19]
Isanbor, C.; O’Hagan, D. Fluorine in medicinal chemistry: A review of anti-cancer agents. J. Fluor. Chem., 2006, 1227, 303-319.
[20]
Stepanovic, S.; Vukovic, D.; Dakic, I.; Savic, B.; Svabic-Vlahovic, M. Amodified microtiter-plate test for quantification of staphylococcal biofilm formation. J. Microbiol. Methods, 2000, 40, 175-179.
[21]
Walencka, E.; Sadowska, B.; Rozalska, S.; Hryniewicz, W.; Rózalska, B. Lysostaphin as a potential therapeutic agent for staphylococcal biofilm eradication. Pol. J. Microbiol., 2005, 54, 191-200.
[22]
Ibrahim, S.R.M.; Mohamed, G.A.; Al Haidari, R.A.; Zayed, M.F.; El-Kholy, A.A.; Elkhayat, E.S.; Ross, S.A. Fusarithioamide B, a new benzamide derivative from the endophytic fungus Fusarium chlamydosporium with potent cytotoxic and antimicrobial activities. Bioorganic. Med. Chem., 2018, 26, 786-790.
[23]
Wiegand, I.; Hilpert, K.; Hancock, R.E.W. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat. Protoc., 2008, 3, 163-175.
[24]
Berman, H.M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E. The protein data bank. Nucleic Acids Res., 2000, 28, 235-242.
[25]
Chemical Computing Group. Molecular Operating Environment (MOE); Chemical Computing Group: Montreal, QC, Canada, 2013; Available online:. http://www.chemcomp.com (accessed on 7 February 2013).

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