Main Article Content
Abstract
In present study, fluorinated piperazine and benzonitrile/nicotinonitrile fused quinazoline derivatives have synthesized, characterized using FT-IR, 1H & 13C NMR, 19F NMR and MS analysis and evaluated as potential antibacterial agents. They were also tested against the multidrug resistant strains. The antibacterial activity results revealed that the majority of synthesized compounds exhibited potential antibacterial with the extraordinary level of minimum inhibitory concentrations comparable to the control drugs. Moreover, the influence of presence or absence of fluoro and trifluoromethyl functional groups on the piperazine ring systems towards different biological species is elaborated. The synthesized compounds were also found non-toxic on the human cervical (HeLa) cells at their minimum inhibitory concentrations.
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Article Details
References
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- H. Wang, C. Wei, X. Deng, F. Li and Z. Quan, Synthesis and Evaluation on Anticonvulsant and Antidepressant Activities of 5-Alkoxy-tetrazolo-[1,5-a]quinazolines, Arch. Pharm., 342, 671 (2009); https://doi.org/10.1002/ardp.200900119
- Clinical and Laboratory Standards Institute, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. Approved Standard M7eA6, Clinical and Laboratory Standards Institute, Wayne, PA, USA (2003).
- P.S. Sagar, U.N. Das, R. Koratkar, G. Ramesh, M. Padma and G.S. Kumar, Cytotoxic Action of cis-Unsaturated Fatty Acids on Human Cervical Carcinoma (HeLa) Cells: Relationship to Free Radicals and Lipid Peroxidation and its Modulation by Calmodulin Antagonists, Cancer Lett., 63, 189 (1992); https://doi.org/10.1016/0304-3835(92)90260-3
- R.M. Kumbhare, T. Dadmal, U. Kosurkar, V. Sridhar and J.V. Rao, Synthesis and Cytotoxic Evaluation of Thiourea and N-bis-Benzothiazole Derivatives: A Novel Class of Cytotoxic Agents, Bioorg. Med. Chem. Lett., 22, 453 (2012); https://doi.org/10.1016/j.bmcl.2011.10.106
- S. Kumar, N. Shakya, S. Gupta, J. Sarkar and D.P. Sahu, Synthesis and Biological Evaluation of Novel 4-(Hetero) Aryl-2-piperazinoquinazolines as Anti-leishmanial and Anti-proliferative agents, Bioorg. Med. Chem. Lett., 19, 2542 (2009); https://doi.org/10.1016/j.bmcl.2009.03.020
- V.J. Ram, B.K. Farhanullah, B.K. Tripathi and A.K. Srivastava, Synthesis and Antihyperglycemic Activity of Suitably Functionalized 3H-Quinazolin-4-ones, Bioorg. Med. Chem., 11, 2439 (2003); https://doi.org/10.1016/S0968-0896(03)00142-1
- Z.-S. Zeng, Q.-Q. He, Y.-H. Liang, X.-Q. Feng, F.-E. Chen, E.D. Clercq, J. Balzarini and C. Pannecouque, Hybrid Diarylbenzopyrimidine Non-nucleoside Reverse Transcriptase Inhibitors as Promising New Leads for Improved Anti-HIV-1 Chemotherapy, Bioorg. Med. Chem., 18, 5039 (2010); https://doi.org/10.1016/j.bmc.2010.05.081
- I. Pogorelic, M. Filipan-Litvic, S. Merkas, G. Ljubic, I. Cepanec and M.J. Litvic, Rapid, Efficient and Selective Reduction of Aromatic Nitro Compounds with Sodium Borohydride and Raney Nickel, Mol. Catal. Chem., 274, 202 (2007); https://doi.org/10.1016/j.molcata.2007.05.020
References
P. Verhaeghe, N. Azas, M. Gasquet, S. Hutter, C. Ducros, M. Laget, S. Rault, P. Rathelot and P. Vanelle, Synthesis and Antiplasmodial Activity of New 4-Aryl-2-trichloromethylquinazolines, Bioorg. Med. Chem. Lett., 18, 396 (2008); https://doi.org/10.1016/j.bmcl.2007.10.027
L.-P. Peng, S. Nagarajan, S. Rasheed and C.-H. Zhou, Synthesis and Biological Evaluation of a New Class of Quinazolinoneazoles as Potential Antimicrobial Agents and Their Interactions with Calf Thymus DNA and Human Serum Albumin, Med. Chem. Commun., 6, 222 (2015); https://doi.org/10.1039/C4MD00281D
L.F. Kuyper, D.P. Baccanari, M.L. Jones, R.N. Hunter, R.L. Tansik, S.S. Joyner, C.M. Boytos, S.K. Rudolph, V. Knick, H.R. Wilson, J.M. Caddell, H.S. Friedman, J.C. Comley and J.N. Stables, High-Affinity Inhibitors of Dihydrofolate Reductase: Antimicrobial and Anticancer Activities of 7,8-Dialkyl-1,3-diaminopyrrolo[3,2-f]quinazolines with Small Molecular Size, J. Med. Chem., 39, 892 (1996); https://doi.org/10.1021/jm9505122
Q. Chao, L. Deng, H. Shih, L.M. Leoni, D. Genini, D.A. Carson and H.B. Cottam, Substituted Isoquinolines and Quinazolines as Potential Antiinflammatory Agents. Synthesis and Biological Evaluation of Inhibitors of Tumor Necrosis Factor a, J. Med. Chem., 42, 3860 (1999); https://doi.org/10.1021/jm9805900
V. Alagarsamy, V. Raja Solomon, M. Murugan, K. Dhanabal, P. Parthiban and G.V. Anjana, Design and Synthesis of 3-(4-Ethylphenyl)-2-substituted amino-3H-quinazolin-4-ones as a Novel Class of Analgesic and Anti-inflammatory Agents, J. Enzyme Inhib. Med. Chem., 23, 839 (2008); https://doi.org/10.1080/14756360701746229
A. Baba, N. Kawamura, H. Makino, Y. Ohta, S. Taketomi and T. Sohda, Studies on Disease-Modifying Antirheumatic Drugs: Synthesis of Novel Quinoline and Quinazoline Derivatives and their Anti-inflammatory Effect, J. Med. Chem., 39, 5176 (1996); https://doi.org/10.1021/jm9509408
A.S. El-Azab and K.E.H. El-Tahir, Synthesis and Anticonvulsant Evaluation of Some New 2,3,8-Trisubstituted-4(3H)-quinazoline Derivatives, Bioorg. Med. Chem. Lett., 22, 327 (2012); https://doi.org/10.1016/j.bmcl.2011.11.007
V. Jatav, P. Mishra, S. Kashaw and J.P. Stables, CNS Depressant and Anticonvulsant Activities of Some Novel 3-[5-Substituted 1,3,4-Thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones, Eur. J. Med. Chem., 43, 1945 (2008); https://doi.org/10.1016/j.ejmech.2007.12.003
M. Ismail, S. Barker, D. Abou El Ella, K. Abouzid, R. Toubar and M. Todd, Design and Synthesis of New Tetrazolyl- and Carboxybiphenyl-ylmethylquinazolin-4-one Derivatives as Angiotensin II AT1 Receptor Antagonists, J. Med. Chem., 49, 1526 (2006); https://doi.org/10.1021/jm050232e
K.S. Jain, J.B. Bariwal, M.K. Kathiravan, M.S. Phoujdar, R.S. Sahne, B.S. Chauhan, A.K. Shah and M.R. Yadav, Recent Advances in Selective a1-Adrenoreceptor Antagonists as Antihypertensive Agents, Bioorg. Med. Chem., 16, 4759 (2008); https://doi.org/10.1016/j.bmc.2008.02.091
M.S. Malamas and J. Millen, Quinazolineacetic Acids and Related Analogs as Aldose Reductase Inhibitors, J. Med. Chem., 34, 1492 (1991); https://doi.org/10.1021/jm00108a038
R. Al-Salahi, R. Ahmad, E. Anouar, N.I.I.N. Azman, M. Marzouk and H.A. Abuelizz, 3-Benzyl(phenethyl)-2-thioxobenzo[g]quinazolines as A New Class of Potent a-Glucosidase Inhibitors: Synthesis and Molecular Docking Study, Future Med. Chem., 10, 1889 (2018); https://doi.org/10.4155/fmc-2018-0141
B. Marvania, P.C. Lee, R. Chaniyara, H. Dong, S. Suman, R. Kakadiya, T.C. Chou, T.C. Lee, A. Shah and T.L. Su, Design, Synthesis and Antitumor Evaluation of Phenyl N-Mustard-Quinazoline Conjugates, Bioorg. Med. Chem., 19, 1987 (2011); https://doi.org/10.1016/j.bmc.2011.01.055
A. Chilin, M.T. Conconi, G. Marzaro, A. Guiotto, L. Urbani, F. Tonus and P. Parnigotto, Exploring Epidermal Growth Factor Receptor (EGFR) Inhibitor Features: The Role of Fused Dioxygenated Rings on the Quinazoline Scaffold, J. Med. Chem., 53, 1862 (2010); https://doi.org/10.1021/jm901338g
T.S. Patel, S.F. Vanparia, S.A. Gandhi, U.H. Patel, R.B. Dixit, C.J. Chudasama and B.C. Dixit, Novel Stereoselective 2,3-Disubstituted Quinazoline-4(3H)-one Derivatives Derived from Glycine as a Potent Antimalarial Lead, New J. Chem., 39, 8638 (2015); https://doi.org/10.1039/C5NJ01408E
T. Fröhlich, C. Reiter, M.M. Ibrahim, J. Beutel, C. Hutterer, I. Zeitträger, H. Bahsi, M. Leidenberger, O. Friedrich, B. Kappes, T. Efferth, M. Marschall and S.B. Tsogoeva, Synthesis of Novel Hybrids of Quinazoline and Artemisinin with High Activities against Plasmodium falciparum, Human Cytomegalovirus and Leukemia Cells, ACS Omega, 2, 2422 (2017); https://doi.org/10.1021/acsomega.7b00310
N.M. Chhatriwala, A.B. Patel, R.V. Patel and P. Kumari, in vitro Biological Investigations of Novel Piperazine Based Heterocycles, J. Chem. Res., 38, 611 (2014); https://doi.org/10.3184/174751914X14116443659287
M.A. Bhat, M.A. Al-Omar, H.A. Ghabbour and A.M. Naglah, A One-Pot Biginelli Synthesis and Characterization of Novel Dihydropyrimi-dinone Derivatives Containing Piperazine/Morpholine Moiety, Molecules, 23, 1559 (2018); https://doi.org/10.3390/molecules23071559
P. Chaudhary, R. Kumar, A.K. Verma, D. Singh, V. Yadav, A.K. Chhillar, G.L. Sharma and R. Chandra, Synthesis and Antimicrobial Activity of N-Alkyl and N-Aryl Piperazine Derivatives, Bioorg. Med. Chem., 14, 1819 (2006); https://doi.org/10.1016/j.bmc.2005.10.032
M.L. Gao, J. Zeng, X. Fang, J. Luo, Z. Jin, Y.H. Liu and Y.Z. Tang, Design, Synthesis and Antibacterial Evaluation of Novel Pleuromutilin Derivatives Possessing Piperazine Linker, Eur. J. Med. Chem., 127, 286 (2017); https://doi.org/10.1016/j.ejmech.2017.01.004
S.F. Wang, Y. Yin, F. Qiao, X. Wu, S. Sha, L. Zhang and H.L. Zhu, Synthesis, Molecular Docking and Biological Evaluation of Metroni-dazole Derivatives Containing Piperazine Skeleton as Potential Anti-bacterial Agents, Bioorg. Med. Chem., 22, 2409 (2014); https://doi.org/10.1016/j.bmc.2014.03.004
S.F. Wang, Y. Yin, X. Wu, F. Qiao, S. Sha, P.C. Lv, J. Zhao and H.L. Zhu, Synthesis, Molecular Docking and Biological Evaluation of Coumarin Derivatives Containing Piperazine Skeleton as Potential Antibacterial Agents, Bioorg. Med. Chem., 22, 5727 (2014); https://doi.org/10.1016/j.bmc.2014.09.048
A.B. Patel, K.H. Chikhalia and P. Kumari, Facile Synthesis of Benzonitrile/Nicotinonitrile based S-Triazines as New Potential Antimycobacterial Agents, Eur. J. Med. Chem., 79, 57 (2014); https://doi.org/10.1016/j.ejmech.2014.03.085
S. Selvarani and P. Rajakumar, Synthesis and Antibacterial Activity of Some Novel Piperazinophanes with an Intraannular Ester Functionality, New J. Chem., 40, 9494 (2016); https://doi.org/10.1039/C6NJ01956K
L. Zhu, J. Jin, C. Liu, C. Zhang, Y. Sun, Y. Guo, D. Fu, X. Chen and B. Xu, Synthesis and Biological Evaluation of Novel Quinazoline-derived Human Pin1 Inhibitors, Bioorg. Med. Chem., 19, 2797 (2011); https://doi.org/10.1016/j.bmc.2011.03.058
K. Kanuma, K. Omodera, M. Nishiguchi, T. Funakoshi, S. Chaki, Y. Nagase, I. Iida, J. Yamaguchi, G. Semple, T. Tran and Y. Sekiguchi, Identification of 4-Amino-2-cyclohexylaminoquinazolines as Metabolically Stable Melanin-Concentrating Hormone Receptor 1 Antagonists, Bioorg. Med. Chem., 14, 3307 (2006); https://doi.org/10.1016/j.bmc.2005.12.052
A.B. Patel and R.M. Raval, Discovery of New Coumarin Substituted Quinazolines as Potential Bioactive Agents, Res. Chem. Intermed., 42, 2163 (2016); https://doi.org/10.1007/s11164-015-2140-0
H. Wang, C. Wei, X. Deng, F. Li and Z. Quan, Synthesis and Evaluation on Anticonvulsant and Antidepressant Activities of 5-Alkoxy-tetrazolo-[1,5-a]quinazolines, Arch. Pharm., 342, 671 (2009); https://doi.org/10.1002/ardp.200900119
Clinical and Laboratory Standards Institute, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. Approved Standard M7eA6, Clinical and Laboratory Standards Institute, Wayne, PA, USA (2003).
P.S. Sagar, U.N. Das, R. Koratkar, G. Ramesh, M. Padma and G.S. Kumar, Cytotoxic Action of cis-Unsaturated Fatty Acids on Human Cervical Carcinoma (HeLa) Cells: Relationship to Free Radicals and Lipid Peroxidation and its Modulation by Calmodulin Antagonists, Cancer Lett., 63, 189 (1992); https://doi.org/10.1016/0304-3835(92)90260-3
R.M. Kumbhare, T. Dadmal, U. Kosurkar, V. Sridhar and J.V. Rao, Synthesis and Cytotoxic Evaluation of Thiourea and N-bis-Benzothiazole Derivatives: A Novel Class of Cytotoxic Agents, Bioorg. Med. Chem. Lett., 22, 453 (2012); https://doi.org/10.1016/j.bmcl.2011.10.106
S. Kumar, N. Shakya, S. Gupta, J. Sarkar and D.P. Sahu, Synthesis and Biological Evaluation of Novel 4-(Hetero) Aryl-2-piperazinoquinazolines as Anti-leishmanial and Anti-proliferative agents, Bioorg. Med. Chem. Lett., 19, 2542 (2009); https://doi.org/10.1016/j.bmcl.2009.03.020
V.J. Ram, B.K. Farhanullah, B.K. Tripathi and A.K. Srivastava, Synthesis and Antihyperglycemic Activity of Suitably Functionalized 3H-Quinazolin-4-ones, Bioorg. Med. Chem., 11, 2439 (2003); https://doi.org/10.1016/S0968-0896(03)00142-1
Z.-S. Zeng, Q.-Q. He, Y.-H. Liang, X.-Q. Feng, F.-E. Chen, E.D. Clercq, J. Balzarini and C. Pannecouque, Hybrid Diarylbenzopyrimidine Non-nucleoside Reverse Transcriptase Inhibitors as Promising New Leads for Improved Anti-HIV-1 Chemotherapy, Bioorg. Med. Chem., 18, 5039 (2010); https://doi.org/10.1016/j.bmc.2010.05.081
I. Pogorelic, M. Filipan-Litvic, S. Merkas, G. Ljubic, I. Cepanec and M.J. Litvic, Rapid, Efficient and Selective Reduction of Aromatic Nitro Compounds with Sodium Borohydride and Raney Nickel, Mol. Catal. Chem., 274, 202 (2007); https://doi.org/10.1016/j.molcata.2007.05.020