QSAR analysis of 1,3-diaryl-2-propen-1-ones and their indole analogs for designing potent antibacterial agents
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Neela Bhatia
,
Kakasaheb Mahadik
Abstract
A series of 1,3-diaryl-2-propen-1-ones and their indole analogs were synthesized and evaluated for antibacterial activity. Structures of newly synthesized compounds were confirmed by physicochemical, spectral and elemental analysis. All the compounds were screened for their antibacterial activities against four different bacterial strains. The QSAR studies were performed using Vlife MDS 3.5 software. QSAR equation revealed that selected electronic, steric and lipophilic parameters have good correlation with antibacterial activity. Best equations were selected on basis of the correlation coefficient (r 2) and the predictable ability of the equations. The present findings suggest that the 1,3-diaryl-2-propen-1-ones framework is an attractive template for structure optimization to achieve higher potency, lower toxicity, and a wider spectrum of antibacterial activity.
[1] Al-Omran, F., & El-Khair, A. A. (2004). Synthesis of polyfunctionally substituted heteroaromatic compounds via benzotriazolyl chalcones with antimicrobial and antifungal activities. Journal of Heterocyclic Chemistry, 41, 327–333. http://dx.doi.org/10.1002/jhet.557041030410.1002/jhet.5570410304Suche in Google Scholar
[2] Audry, E., Dubost, J. P., Colleter, J. C., & Dallet, P. (1986). A new approach to structure-activity relations: the molecular lipophilicity potential. European Journal of Medicinal Chemistry, 21, 71–72. Suche in Google Scholar
[3] Berber, I., Cokmus, C., & Atalan, E. (2003). Characterization of Staphylococcus species by SDS-PAGE of whole cell and extracellular proteins. Microbiology, 72, 54–57. DOI: 10.1023/A:1022221905449. http://dx.doi.org/10.1023/A:102222190544910.1023/A:1022221905449Suche in Google Scholar
[4] Deng, J., Sanchez, T., Al-Mawsawi, L. Q., Dayam, R., Yunes, R. A., Garofalo, A., Bolger, M. B., & Neamati, N. (2007). Discovery of structurally diverse HIV-1 integrase inhibitors based on a chalcone pharmacophore. Bioorganic & Medicinal Chemistry, 15, 4985–5002. DOI: 10.1016/j.bmc.2007.04.041. http://dx.doi.org/10.1016/j.bmc.2007.04.04110.1016/j.bmc.2007.04.041Suche in Google Scholar
[5] Furniss, B. S., Hannaford, A. J., Smith, P. W. G., & Tatchell, A. R. (1989). Vogel’s textbook of practical organic chemistry, (5th ed., p. 1034.). London: Longman Scientific & Technical. Suche in Google Scholar
[6] Gasull, E. I., Silber, J. J., Blanco, S. E., Tomas, F., & Ferretti, F. H. (2000). A theoretical and experimental study of the formation mechanism of 4-X-chalcones by the Claisen-Schmidt reaction. Journal of Molecular Structure: THEOCHEM, 503, 131–144. DOI: 10.1016/S0166-1280(99)00256-0. http://dx.doi.org/10.1016/S0166-1280(99)00256-010.1016/S0166-1280(99)00256-0Suche in Google Scholar
[7] Hall, L. H., & Kier, L. B. (1991). The molecular connectivity chi indexes and kappa shape indexes in structure-property modeling. In K. B. Lipkowitz & D. B. Boyd (Eds.), Reviews of computational chemistry (Vol. 2, Chap. 9, pp. 367–422). New York: VCH Publishers. DOI: 002/9780470125793.ch9. http://dx.doi.org/10.1002/9780470125793.ch910.1002/9780470125793.ch9Suche in Google Scholar
[8] Hasan, A., Khan, K. M., Sher, M., Maharvi, G. M., Nawaz, S. A., Choudhary, M. I., Atta-ur-Rahman, & Supuran, C. T. (2005). Synthesis and inhibitory potential towards acetylcholinesterase, butyrylcholinesterase and lipoxigenase of some variably substituted chalcones. Journal of Enzyme Inhibition and Medicinal Chemistry, 20, 41–47. DOI: 10.1080/14756360400015231. http://dx.doi.org/10.1080/1475636040001523110.1080/14756360400015231Suche in Google Scholar
[9] Herencia, F., Ferrándiz, M. L., Ubeda, A., Dominguez, J. N., Charris, J. E., Lobo, G. M., & Alcaraz, M. J. (1998). Synthesis and anti-inflammatory activity of chalcone derivatives. Bioorganic & Medicinal Chemistry Letters, 8, 1169–1174. DOI: 10.1016/S0960-894X(98)00179-6. http://dx.doi.org/10.1016/S0960-894X(98)00179-610.1016/S0960-894X(98)00179-6Suche in Google Scholar
[10] Herencia, F., Lopez-Garcia, M. P., Ubeda, A., & Ferrándiz, M. L. (2002). Nitric oxide-scavenging properties of some chalcone derivatives. Nitric Oxide: Biology and Chemistry, 6, 242–246. DOI: 10.1006/niox.2001.0396. http://dx.doi.org/10.1006/niox.2001.039610.1006/niox.2001.0396Suche in Google Scholar PubMed
[11] Khan, M. S. Y., & Hasan, S. M. (2003). Synthesis, antiinflammatory and antibacterial activity of some new flavonoidal derivatives. Indian Journal of Chemistry, Section B, 42, 1970–1974. 10.1002/chin.200348127Suche in Google Scholar
[12] Kier, L. B., & Hall, L. H. (1977). The nature of structure-activity relationships and their relation to molecular connectivity. European Journal of Medicinal Chemistry, 12, 307–312. Suche in Google Scholar
[13] Lahtchev, K. L., Batovska, D. I., Parushev, St. P., Ubiyvovk, V. M., & Sibirny, A. A. (2008). Antifungal activity of chalcones: A mechanistic study using various yeast strains. European Journal of Medicinal Chemistry, 43, 2220–2228. DOI: 10.1016/j.ejmech.2007.12.027. http://dx.doi.org/10.1016/j.ejmech.2007.12.02710.1016/j.ejmech.2007.12.027Suche in Google Scholar PubMed
[14] Lee, V. J., & Hecker, S. J. (1999). Antibiotic resistance versus small molecules, the chemical evolution. Medicinal Research Reviews, 19, 521–542. DOI: 10.1002/(SICI)1098-1128(199911)19:6<521::AID-MED4>3.0.CO;2-9. http://dx.doi.org/10.1002/(SICI)1098-1128(199911)19:6<521::AID-MED4>3.0.CO;2-910.1002/(SICI)1098-1128(199911)19:6<521::AID-MED4>3.0.CO;2-9Suche in Google Scholar
[15] Liu, M., Wilairat, P., Croft, S. L., Tan, A. L-C., & Go, ML. (2003). Structure-activity relationships of antileishmanial and antimalarial chalcones. Bioorganic & Medicinal Chemistry, 11, 2729–2738. DOI: 10.1016/S0968-0896(03)00233-5. http://dx.doi.org/10.1016/S0968-0896(03)00233-510.1016/S0968-0896(03)00233-5Suche in Google Scholar
[16] López, S. N., Castelli, M. V., Zacchino, S. A., Dominguez, J. N., Lobo, G., Charris-Charris, J., Cortes, J. C. G., Ribas, J. C., Devia, C., Rodriguez, A. M., & Enriz, R. D. (2001). In vitro antifungal evaluation and structure.activity relationships of a new series of chalcone derivatives and synthetic analogues, with inhibitory properties against polymers of the fungal cell wall. Bioorganic & Medicinal Chemistry, 9, 1999–2013. DOI: 10.1016/S0968-0896(01)00116-X. http://dx.doi.org/10.1016/S0968-0896(01)00116-X10.1016/S0968-0896(01)00116-XSuche in Google Scholar
[17] Mishra, N., Arora, P., Kumar, B., Mishra, L. C., Bhattacharya, A., Awasthi S. K., & Bhasin, V. K. (2008). Synthesis of novel substituted 1,3-diaryl propenone derivatives and their antimalarial activity in vitro. European Journal of Medicinal Chemistry, 43, 1530–1535. DOI: 10.1016/j.ejmech.2007.09.014. http://dx.doi.org/10.1016/j.ejmech.2007.09.01410.1016/j.ejmech.2007.09.014Suche in Google Scholar
[18] Mitscher, L. A., Pillai, S. P., Gentry, E. J., & Shankel, D. M. (1999). Multiple drug resistance. Medicinal Research Reviews, 19, 477–496. DOI: 10.1002/(SICI)1098-1128(199911)19:6<477::AID-MED2>3.0.CO;2-W. http://dx.doi.org/10.1002/(SICI)1098-1128(199911)19:6<477::AID-MED2>3.0.CO;2-W10.1002/(SICI)1098-1128(199911)19:6<477::AID-MED2>3.0.CO;2-WSuche in Google Scholar
[19] Nowakowska, Z. (2007). A review of anti-infective and anti-inflammatory chalcones. European Journal of Medicinal Chemistry, 42, 125–137. DOI: 10.1016/j.ejmech.2006.09.019. http://dx.doi.org/10.1016/j.ejmech.2006.09.01910.1016/j.ejmech.2006.09.019Suche in Google Scholar
[20] Ono, M., Hori, M., Haratake, M., Tomiyama, T., Mori, H., & Nakayama, M. (2007). Structure.activity relationship of chalcones and related derivatives as ligands for detecting of β-amyloid plaques in the brain. Bioorganic & Medicinal Chemistry, 15, 6388–6396. DOI: 10.1016/j.bmc.2007.06.055. http://dx.doi.org/10.1016/j.bmc.2007.06.05510.1016/j.bmc.2007.06.055Suche in Google Scholar
[21] Pellerin, J. L., Bourdeau, P., Sebbag, H., & Person, J. M. (1998). Epidemiosurveillance of antimicrobial compound resistance of Staphylococcus intermedius clinical isolates from canine pyodermas. Comparative Immunology Microbiology & Infectious Diseases, 21, 115–133. DOI: 10.1016/S0147-9571(97)00026-X. http://dx.doi.org/10.1016/S0147-9571(97)00026-X10.1016/S0147-9571(97)00026-XSuche in Google Scholar
[22] Sivakumar, P. M., Prabu Seenivasan, S., Kumar, V., & Doble, M. (2007). Synthesis, antimycobacterial activity evaluation, and QSAR studies of chalcone derivatives. Bioorganic & Medicinal Chemistry Letters, 17, 1695–1700. DOI: 10.1016/j.bmcl.2006.12.112. http://dx.doi.org/10.1016/j.bmcl.2006.12.11210.1016/j.bmcl.2006.12.112Suche in Google Scholar
[23] Solankee, A., & Patel, J. (2004). Synthesis of chalcones, pyrazolines, aminopyrimidines and pyrimidinethiones as antibacterial agents. Indian Journal of Chemistry, Section B, 43, 1580–1584. Suche in Google Scholar
[24] Sung, W. S., Jung, H. J., Park, K., Kim, H. S., Lee, I-S., & Lee, D. G. (2007). 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF); antimicrobial compound with cell cycle arrest in nosocomial pathogens. Life Sciences, 80, 586–591. DOI: 10.1016/j.lfs.2006.10.008. http://dx.doi.org/10.1016/j.lfs.2006.10.00810.1016/j.lfs.2006.10.008Suche in Google Scholar
[25] Xu, Y. C., Leung, S. W. S., Yeung, D. K. Y., Hu, L. H., Chen, G. H., Che, C. M., & Man, R. Y. K. (2007). Structure. activity relationships of flavonoids for vascular relaxation in porcine coronary artery. Phytochemistry, 68, 1179–1188. DOI: 10.1016/j.phytochem.2007.02.013. http://dx.doi.org/10.1016/j.phytochem.2007.02.01310.1016/j.phytochem.2007.02.013Suche in Google Scholar PubMed
© 2009 Institute of Chemistry, Slovak Academy of Sciences
Artikel in diesem Heft
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Artikel in diesem Heft
- GC-MS analyses of flower ether extracts of Prunus domestica L. and Prunus padus L. (Rosaceae)
- A novel kinetic-spectrophotometric method for determination of nitrites in water
- Characterization of recombinant antibodies for detection of TNT and its derivatives
- Improvements in the selection of real components forming a substitute mixture for petroleum fractions
- Chemical evaluation of seeded fruit biomass of oil pumpkin (Cucurbita pepo L. var. Styriaca)
- Application of 31P NMR for added polyphosphate determination in pork meat
- Estimation of composition, coordination model, and stability constant of some metal/phosphate complexes using spectral and potentiometric measurements
- Synthesis, characterization, and anti-tumor activities of some transition metal(II) complexes with podophyllic acid hydrazide
- Artificial neural network prediction of steric hindrance parameter of polymers
- Immobilization of porphyrins in poly(hydroxymethylsiloxane)
- Preparation and characterization of porous cordierite for potential use in cellular ceramics
- Characterization of NiFe2O4 nanoparticles synthesized by various methods
- QSAR analysis of 1,3-diaryl-2-propen-1-ones and their indole analogs for designing potent antibacterial agents
- QSAR study of 2,4-disubstituted phenoxyacetic acid derivatives as a CRTh2 receptor antagonists
- Comparison of isothermal and non-isothermal chemiluminescence and differential scanning calorimetry experiments with benzoyl peroxide
- Wettability of plasma-polymerized vinyltriethoxysilane film
- A spectrofluorimetric method for the determination of acitretin in pharmaceuticals
- Fatty acid profile of Trichosanthes kirilowii Maxim. seed oil
- Determination of the enthalpy of fusion of K3TaO2F4 and KTaF6
