TY  - JOUR
T1  - Synthesis and Anti-Biofilm Activity Studies on Novel Quinazolinone-Thiadiazole Hybrids
AU  - Türk, Sevda
AU  - Ulusoy, Seyhan
AU  - Karakuş, Sevgi
AU  - Tınaz, Gülgün
PY  - 2025
DA  - March
Y2  - 2025
DO  - 10.33808/clinexphealthsci.1548035
JF  - Clinical and Experimental Health Sciences
PB  - Marmara University
WT  - DergiPark
SN  - 2459-1459
SP  - 170
EP  - 174
VL  - 15
IS  - 1
LA  - en
AB  - Objective: In this study it was aimed to synthesize novel 1,3,4-thiadizole bearing 4(3H)-quinazolinone compounds, elucidate their structure and evaluate their anti-biofilm activity.Methods: Four novel 4(3H)-quinazolinone compounds (1-4) were synthesized with a two step reaction starting from 5-bromoanthranilic acid. Their anti-biofilm activity was investigated.Results: The final compounds’ structures were clarified by elemental analysis and spectroscopic methods (IR, 1H-NMR, 13C-NMR and MS). In the result of anti-biofilm activity studies, they possessed 26.0-30.0% biofilm formation inhibition.Conclusion: Among the tested compounds, 6-bromo-3-{4-[5-(4-nitrophenylamino)-1,3,4-thiadiazol-2-yl]phenyl}-2-methylquinazolin-4(3H)-one formulated compound 3 was found as the most active one with 30.0% biofilm formation inhibition.
KW  - 4(3H)-Quinazolinones
KW  - 1-3-4-thiadiazoles
KW  - anti-biofilm activity
KW  - P. aeruginosa
CR  - Gupta P, Gupta RK, Harjai K. Multiple virulence factors regulated by quorum sensing may help in establishment and colonisation of urinary tract by Pseudomonas aeruginosa during experimental urinary tract infection. Indian J Med Microbiol. 2013; 31(1): 29-33. https://doi.org/10.4103/0255-0857.108715
CR  - Brindhadevi K, LewisOscar F, Mylonakis E, Shanmugam S, Verma TN, Pugazhendhi A. Biofilm and Quorum sensing mediated pathogenicity in Pseudomonas aeruginosa. Process Biochem. 2020; 96: 49-57. https://doi.org/10.1016/j.procbio.2020.06.001
CR  - Rodriguez-Urretavizcaya B, Vilaplana L, Marco MP. Strategies for Quorum Sensing inhibition as a tool for controlling Pseudomonas aeruginosa infections. Int J Antimicrob Agents. 2024 August 29. [Epub ahead of print]. https://doi.org/10.1016/j.ijantimicag.2024.107323
CR  - Zalcberg J. Overview of the tolerability of ‘Tomudex’ (raltitrexed) collective clinical experience in advanced colorectal cancer. Anti-Cancer Drugs. 1997; 8(2): 17-22. https://doi.org/10.1097/00001813-199708002-00004
CR  - Cutsem EV, Cunningham D, Maroun, J, Cervantes, A, Glimelius, B. Raltitrexed: current clinical status and future directions. Ann Oncol. 2002; 13: 513-522. https://doi.org/10.1093/annonc/mdf054
CR  - Fozard JR. Mechanism of the hypotensive effect of Ketanserin. J Cardiovasc Pharmacol. 1982; 4(5): 829-838. https://doi.org/10.1097/00005344-198209000-00020
CR  - Irannejad H, Emami S, Mirzaei H, Hashemi SM. Data on molecular docking of tautomers and enantiomers of ATTAF-1 and ATTAF-2 selectivity to the human/fungal lanosterol-14 α-demethylase. Data Brief. 2020; 31: 105942. https://doi.org/10.1016/j.dib.2020.105942
CR  - Cao X, Xu Y, Cao Y, Wang R, Zhou R, Chu W, Yang Y. Design, synthesis, and structure activity relationship studies of novel thienopyrrolidone derivatives with strong antifungal activity against Aspergillus fumigates. Eur J Med Chem. 2015; 102: 471-476. https://doi.org/10.1016/j.ejmech.2015.08.023
CR  - Ding Z, Nib T, Xie F, Hao Y, Yu S, Chai X, Jin Y, Wang T, Jian Y, Zhang D. Design, synthesis, and structure-activity relationship studies of novel triazole agents with strong antifungal activity against Aspergillus fumigatus. Bioorg Med Chem Lett. 2020; 30: 126951. https://doi.org/10.1016/j.bmcl.2020.126951
CR  - Baranauskiene L, Skiudaite L, Michailoviene V, Petrauskas V, Matulis D. Thiazide and other Cl-benzenesulfonamide bearing clinical drug affinities for human carbonic anhydrases. PLoS One 2021; 16(6): e0253608. https://doi.org/10.1371/journal.pone.0253608
CR  - Sen D, Banerjee A, Ghosh AK, Chatterjee TK. Synthesis and antimalarial evaluation of some 4-quinazolinone derivatives based on febrifugine. J Adv Pharm Tech Res. 2010; 1(4): 401-405. https://doi.org/10.4103/0110-5558.76439
CR  - Back H, Pradhan S, Yoon Y, Kang W, Chae J, Han N, Miki N, Kwon K, Kim S, Yun H. Population pharmacokinetic modeling and simulation of Afloqualone to predict steady-state exposure levels. Int J Pharmacol. 2018; 14(2): 276-284. https://doi.org/10.3923/ijp.2018.276.284
CR  - Hussain MA, Chiu AT, Price WA, Timmermans PB, Shefter E. Anthihypertensive activity of 2-[(2-hydroxyphenyl)amino]-4(3H)-quinazolinone. Pharm Res. 1988; 5(4): 242-244. https://doi.org/10.1023/a:1015949931218
CR  - Rathod B, Joshi S, Regu S, Manikanta KVNS, Kumar H, Dubey S, Chowdhury A, Shaikh RP, Das A, Patel S, Satvase R, Chatterjee DR, Jain A, Garg R, Shard A. Design and synthesis of novel quinazolinone-based pyruvate kinase M2 activators as selective inhibitors of oral cancer cells. J Mol Struct. 2024; 1304: 134595. https://doi.org/10.1016/j.molstruc.2024.137595
CR  - El-Karim SSA, Syam YM, El Kerdawy AM, Abdel-Mohsen HT. Rational design and synthesis of novel quinazolinone N-acetohydrazides as type II multi-kinase inhibitors and potential anticancer agents. Bioorg Chem. 2024; 142: 106920. https://doi.org/10.1016/j.bioorg.2023.106920
CR  - Cheke RS, Shinde SD, Ambhore JP, Chaudhari SR, Bari SB. Quinazoline: An update on current status against convulsions. J Mol Struct. 2022; 1248: 131384. https://doi.org/10.1016/j.molstruc.2021.131384
CR  - Mravljak J, Slavec L,Hrast M, Sova M. Synthesis and evaluation of antioxidant properties of 2-substituted quinazolin-4(3H)-ones. Molecules 2021; 26: 6585. https://doi.org/10.3390/molecules26216585
CR  - Abbas SE, Awadallah FM, Ibrahin NA, Said EG, Kamel GM. New quinazolinone pyrimidine hybrids: Synthesis, anti-inflammatory, and ulcerogenicity studies. Eur J Med Chem. 2012; 53: 141-149. https://doi.org/10.1016/j.ejmech.2012.03.050
CR  - Mhetre UV, Haval NB, Bondle GM, Rathod SS, Choudhari PB, Kumari J, Sriram D, Haval KP. Design, synthesis and molecular docking study of novel triazole-quinazolinone hybrids as antimalarial and antitubercular agents. Bioorg Med Chem Lett. 2024; 108: 129800. https://doi.org/10.1016/j.bmcl.2024.129800
CR  - Hemalatha K, Madhumitha G. Study of binding interaction between anthelmintic 2,3-dihydroquinazolin-4-ones with bovine serum albumin by spectroscopic methods. J Lumin. 2016; 178: 163-171. https://doi.org/10.1016/j.jlumin.2016.05.041
CR  - Alamri MA, Afzal O, Akhtar MJ, Karim S, Husain M, Alossaimi MA, Riadi Y. Synthesis, in silico and in vitro studies of novel quinazolinone derivatives as potential SARS-CoV-2 3CLpro inhibitors. Arab J Chem. 2024; 17: 105384. https://doi.org/10.1016/j.arabjc.2023.105384
CR  - Deng Y, Chen M, Yi J, Zheng Y. Design, synthesis, and anti–tobacco mosaic virus activity evaluation of quinazolinone derivatives containing purine moieties. Phytochem Lett. 2024; 59: 10-14. https://doi.org/10.1016/j.phytol.2023.11.003
CR  - Qhobosheane MA, Legoabe LJ, Petzer A, Petzer JP. The monoamine oxidase inhibition properties of C6-mono- and N3/C6-disubstituted derivatives of 4(3H)-quinazolinone. Bioorg Chem. 2019; 85: 60-65. https://doi.org/10.1016/j.bioorg.2018.12.030
CR  - Khalifa MM, Sakr HM, Ibrahim A, Mansour AM, Ayyad RR. Design and synthesis of new benzylidene-quinazolinone hybrids as potential anti-diabetic agents: In vitro α-glucosidase inhibition, and docking studies. J Mol Struct. 2022; 1250: 131768. https://doi.org/10.1016/j.molstruc.2021.131768
CR  - Tokalı FS, Sağlamtaş R, Öztekin A, Yırtıcı Ü, Çomaklı V. New diacetic acids containing quinazolin-4(3H)-one: Synthesis, characterization, anticholinergic properties, DFT analysis and molecular docking studies. Chemistry Select 2023; 8(e202205039): 1-9. https://doi.org/10.1002/slct.202205039
CR  - Moftah HK, Mousa MHA, Elrazaz EZ, Kamel AS, Lasheen DS, Georgey HH. Novel quinazolinone Derivatives: Design, synthesis and in vivo evaluation as potential agents targeting Alzheimer disease. Bioorg Chem. 2024; 143: 107-065. https://doi.org/10.1016/j.bioorg.2023.107065
CR  - Bouley R, Ding, D, Peng Z, Bastian, M, Lastochkin E, Song W, Suckow MA, Schroeder VA, Wolter WR, Mobashery S, Chang M. Structure−activity relationship for the 4(3H)‑quinazolinone antibacterials. J Med Chem. 2016; 59: 5011-5021. https://doi.org/10.1021/acs.jmedchem.6b00372
CR  - Gatadi S, Lakshmi TV, Nanduri S. 4(3H)-Quinazolinone derivatives: Promising antibacterial drug leads. Eur J Med Chem. 2019; 170: 157-172. https://doi.org/10.1016/j.ejmech.2019.03.018
CR  - Liu T, Peng F, Cao X, Liu F, Wang Q, Liu L, Xue W. Design, synthesis, antibacterial activity, antiviral Activity, and mechanism of myricetin derivatives containing a quinazolinone moiety. ACS Omega 2021; 6: 30826-30833. https://doi.org/10.1021/acsomega.1c05256
CR  - Rasapalli S, Murphy ZF, Sammeta VR, Golen JA, Weig AW, Melander RJ, Melander C, Macha P, Vasudev MC. Synthesis and biofilm inhibition studies of 2-(2-amino-6-arylpyrimidin-4-yl)quinazolin-4(3H)-ones. Bioorg Med Chem Lett. 2020; 30: 127550. https://doi.org/10.1016/j.bmcl.2020.127550
CR  - Rakesh KP, Kumara HK, Ullas BC, Shivakumara J, Gowda DC. Amino acids conjugated quinazolinone-Schiff’s bases as potential antimicrobial agents: Synthesis, SAR and molecular docking studies. Bioorg Chem. 2019; 90: 103093. https://doi.org/10.1016/j.bioorg.2019.103093
CR  - Türk S, Karakuş S, Maryam A, Oruç-Emre EE. Synthesis, characterization, antituberculosis activity and computational studies on novel Schiff bases of 1,3,4-thiadiazole derivatives. J Res Pharm. 2020; 24(6): 793-800. https://doi.org/10.35333/jrp.2020.232
CR  - Kadi AA, El-Brollosy NR, Al-Deeb OA, Habib EE, Ibrahim TM, El-Emam AA. Synthesis, antimicrobial, and anti-inflammatory activities of novel 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles and 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazoles. Eur J Med Chem. 2007; 42: 235-242. https://doi.org/10.1016/j.ejmech.2006.10.003
CR  - Türk S, Karakuş S, Ece A, Ulusoy S, Boşgelmez-Tınaz G. Synthesis, structure elucidation and biological activities of some novel 4(3H)-quinazolinones as anti-biofilm agents. Lett Drug Des Discov. 2019; 16: 313-321. https://doi.org/10.2174/1570180815666180621101123
CR  - Türk S, Turan K, Ulusoy S, Karakuş S, Boşgelmez-Tınaz G. Synthesis, characterization and biological activity studies on amide derivatives. Istanbul J Pharm. 2018; 48(3): 76-81. https://doi.org/10.26650/IstanbulJPharm.2018.18007
CR  - Karakus S, Kocyigit-Kaymakcioglu B, Toklu HZ, Aricioglu F, Rollas S. Synthesis and anticonvulsant activity of new N-(alkyl/substitutedaryl)-N'-4-(5-cyclohexylamino)-1,3,4-thiadiazole-2-yl)phenythioureas. Arch Pharm. 2009; 342(1): 48-53. https://doi.org/10.1002/ardp.200800118
CR  - Ulusoy S, Akalın RB, Çevikbaş H, Berisha A, Oral A, Boşgelmez-Tinaz G. Zeolite 4A as a jammer of bacterial communication in Chromobacterium violaceum and Pseudomonas aeruginosa. Future Microbiol. 2022; 17(11), 861-871.  https://doi.org/10.2217/fmb-2021-0174
CR  - Uraz M, Karakuş S, Mohsen UA, Kaplancıklı ZA, Rollas S. The synthesis and evaluation of anti-acetylcholinesterase activity of some 4(3H)-quinazolinone derivatives bearing substituted 1,3,4-thiadiazole. Marmara Pharm J. 2017; 21: 96-101. https://doi.org/10.12991/marupj.259886
UR  - https://doi.org/10.33808/clinexphealthsci.1548035
L1  - https://dergipark.org.tr/en/download/article-file/4205512
ER  -