Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

The Spectrum of Thiazolidinediones against Respiratory Tract Pathogenic Bacteria: An In Vitro and In Silico Approach

Author(s): Mohammed Al Bratty, Ayman Q. Hakami, Hatim A. Masmali, Md. Shamsher Alam, Hassan A. Alhazmi, Neelaveni Thangavel*, Asim Najmi, Sivakumar S. Moni and Anzarul Haque

Volume 21, Issue 14, 2020

Page: [1457 - 1469] Pages: 13

DOI: 10.2174/1389201021666200618161210

Price: $65

Abstract

Background and Objectives: Drug design strategies to develop novel broad-spectrum antibacterial agents for the treatment of respiratory tract infections that can combat bacterial resistance are currently gaining momentum. 2,4-thiazolidinedione is a structural scaffold that contains pharmacophores similar to β-lactam and non- β-lactam antibiotics. The objective of the study was to synthesize newer 3,5-Disubstituted-2,4-Thiazolidinediones (DTZDs) and subject them to in vitro antibacterial screening against bacterial pathogens. Also, we performed in silico docking of selected compounds to penicillin-binding proteins and beta-lactamases.

Methods: Intermediate Schiff bases were prepared by the reaction between 2,4-thiazolidinedione and an appropriate aldehyde followed by acylation of the ring nitrogen with 3-brompropanoyl chloride resulting in DTZDs. Minimum inhibitory concentrations were determined against few bacteria infecting the respiratory tract by the broth tube dilution method. Zones of inhibitions against the bacteria were also determined using agar well diffusion technique. Molecular docking of the compounds to all types of Penicillin-Binding Proteins (PBPs) and β-lactamases was also carried out.

Results: Compounds DTZD12 and DTZD16 exhibited broad-spectrum antibacterial activity. The minimum inhibitory concentrations of the compounds were 175μg/100μL. Measurements of the zones of inhibitions indicated that compound DTZD12 was more active than DZTD16. E. coli was the most susceptible organism. Docking results established that both the compounds were able to interact with PBPs and β-lactamases through strong hydrogen bonds, especially the unique interaction with active serine residue of the PBP for inhibition of cell wall synthesis.

Conclusion: DTZD12 and DTZD16 can be developed into antibacterial drugs for respiratory tract infections to oppose bacterial resistance, or can also be used as leads for repurposing the existing 2,4- thiazolidinediones.

Keywords: Antibacterial susceptibility, docking, in silico, penicillin-binding protein, respiratory tract infections, thiazolidinediones, β-lactamase resistant.

« Previous Next »
Graphical Abstract

[1]
Sarmah, N.; Sarmah, A.; Das, D.K. A study on the microbiological profile of Respiratory Tract Infection (RTI) in patients attending Gauhati Medical College & Hospital. Ann. Int. Med. Den. Res., 2016, 2(5), 11-14.
[http://dx.doi.org/10.21276/aimdr.2016.2.5.MB3]
[2]
Zervosen, A.; Sauvage, E.; Frère, J-M.; Charlier, P.; Luxen, A. Development of new drugs for an old target: The penicillin binding proteins. Molecules, 2012, 17(11), 12478-12505.
[http://dx.doi.org/10.3390/molecules171112478] [PMID: 23095893]
[3]
Qin, W.; Panunzio, M.; Biondi, S. β-Lactam antibiotics renaissance. Antibiotics (Basel), 2014, 3(2), 193-215.
[http://dx.doi.org/10.3390/antibiotics3020193] [PMID: 27025744]
[4]
Thangavel, N.; Al Bratty, M.; Akhtar Javed, S.; Ahsan, W.; Alhazmi, H.A. Targeting peroxisome proliferator-activated receptors using thiazolidinediones: Strategy for design of novel antidiabetic drugs. Int. J. Med. Chem., 2017, 2017Article no. 1069718
[5]
Thangavel, N.; Bratty, M.A.; Javed, S.A.; Ahsan, W.; Hazmi, H.A. Oxadiazolyl thiazolidinedione as a non-adipogenic PPAR-γ partial agonist and its effect on glucose homeostasis in type 2 diabetes. J. Biol. Regul. Homeost. Agents, 2019, 33(3), 707-719.
[PMID: 31204468]
[6]
Naim, M.J.; Alam, M.J.; Ahmad, S.; Nawaz, F.; Shrivastava, N.; Sahu, M.; Alam, O. Therapeutic journey of 2,4-thiazolidinediones as a versatile scaffold: An insight into structure activity relationship. Eur. J. Med. Chem., 2017, 129, 218-250.
[http://dx.doi.org/10.1016/j.ejmech.2017.02.031] [PMID: 28231521]
[7]
Lange, R.P.; Locher, H.H.; Wyss, P.C.; Then, R.L. The targets of currently used antibacterial agents: Lessons for drug discovery. Curr. Pharm. Des., 2007, 13(30), 3140-3154.
[http://dx.doi.org/10.2174/138161207782110408] [PMID: 17979755]
[8]
Sauvage, E.; Kerff, F.; Terrak, M.; Ayala, J.A.; Charlier, P. The penicillin-binding proteins: Structure and role in peptidoglycan biosynthesis. FEMS Microbiol. Rev., 2008, 32(2), 234-258.
[http://dx.doi.org/10.1111/j.1574-6976.2008.00105.x] [PMID: 18266856]
[9]
Öztürk, H.; Ozkirimli, E.; Özgür, A. Classification of Beta-lactamases and penicillin binding proteins using ligand-centric network models. PLoS One, 2015, 10(2)e0117874
[http://dx.doi.org/10.1371/journal.pone.0117874] [PMID: 25689853]
[10]
Moni, S.S.; Alam, M.F.; Safhi, M.M.; Jabeen, A.; Sanobar, S.; Siddiqui, R.; Moochikkal, R. Potency of nano-antibacterial formulation from Sargassum binderi against selected human pathogenic bacteria. Braz. J. Pharm. Sci., 2018, 54(4)
[http://dx.doi.org/10.1590/s2175-97902018000417811]
[11]
Anderson, A.C. The process of structure-based drug design. Chem. Biol., 2003, 10(9), 787-797.
[http://dx.doi.org/10.1016/j.chembiol.2003.09.002] [PMID: 14522049]
[12]
Jitendra, S.; Nanda, A.; Kaur, S.; Singh, M. A comprehensive molecular interaction map for Hepatitis B virus and drug designing of a novel inhibitor for Hepatitis B X protein. Bioinformation, 2011, 7(1), 9-14.
[http://dx.doi.org/10.6026/97320630007009] [PMID: 21904432]
[13]
Monishi, D.C.; Rupjyoti, S. Essential basic protocol in computer aided drug designing: Efficiency and challenges. IJBB, 2018, 4(4), 77-80.
[14]
Alogheli, H.; Olanders, G.; Schaal, W.; Brandt, P.; Karlén, A. Docking of macrocycles: Comparing rigid and flexible docking in Glide. J. Chem. Inf. Model., 2017, 57(2), 190-202.
[http://dx.doi.org/10.1021/acs.jcim.6b00443] [PMID: 28079375]
[15]
Huang, C.C.; Meng, E.C.; Morris, J.H.; Pettersen, E.F.; Ferrin, T.E. Enhancing UCSF Chimera through web services. Nucleic Acids Res., 2014, 42(Web Server issue), W478-484.
[PMID: 24861624]
[16]
Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461.
[PMID: 19499576]
[17]
Ali, I.; Eisa, T.; Asghar, B.H.; Hojat, B.; Maryam, I. A quantitative structure-activity relationship study of Calpeptin (Calpain inhibitor) as an anticancer agent. J. Chin Chem Soc-TAIP, 2018, 65(11), 1293-1306.
[18]
Nayara, S.R.S.; Luana, K.S.G.; Jonatas, L.D.; Juliane, S.S.; César, F.S.; Francinaldo, S.B.; Raí, C.S.; Josivan, S.C. Hage-Melim.; C.B.R.D.S. Computational analysis of physicochemical, pharmacokinetic and toxicological properties of deoxyhypusine synthase inhibitors with antimalarial activity. Comput. Mol. Biosci., 2014, 4, 47-57.
[http://dx.doi.org/10.4236/cmb.2014.44006]
[19]
Muhammad, A.; Andy-Nur, H.; Henny, K.; Yamin, Y.; Ida, U. Identification of polyketide synthase 13 inhibitor: Pharmacophore-based virtual screening and molecular dynamics simulation. J. Appl. Pharm. Sci., 2019, 9(7), 12-17.
[http://dx.doi.org/10.7324/JAPS.2019.90702]
[20]
Mooers, B.H. Simplifying and enhancing the use of PyMOL with horizontal scripts. Protein Sci., 2016, 25(10), 1873-1882.
[http://dx.doi.org/10.1002/pro.2996] [PMID: 27488983]
[21]
Masadeh, M.M.; Mhaidat, N.M.; Al-Azzam, S.I.; Alzoubi, K.H. Investigation of the antibacterial activity of pioglitazone. Drug Des. Devel. Ther., 2011, 5, 421-425.
[http://dx.doi.org/10.2147/DDDT.S24126] [PMID: 22087061]
[22]
Patel, H.; Sonawane, Y.; Jagtap, R.; Dhangar, K.; Thapliyal, N.; Surana, S.; Noolvi, M.; Shaikh, M.S.; Rane, R.A.; Karpoormath, R. Structural insight of glitazone for hepato-toxicity: Resolving mystery by PASS. Bioorg. Med. Chem. Lett., 2015, 25(9), 1938-1946.
[http://dx.doi.org/10.1016/j.bmcl.2015.03.020] [PMID: 25851939]
[23]
Jing-Bo, J.; James, A.B.; Franci, X.M.; Humaei, H. Thiazolidinediones cause cardiotoxicity via PPAR-γ-independent mechanism. Cardiotoxicity; Tan, W., Ed.; Intech Open Ltd: London, 2018.
[http://dx.doi.org/10.5772/intechopen.78957]
[24]
Nazreen, S.; Alam, M.S.; Hamid, H.; Yar, M.S.; Shafi, S.; Dhulap, A.; Alam, P.; Pasha, M.A.Q.; Bano, S.; Alam, M.M.; Haider, S.; Ali, Y.; Kharbanda, C.; Pillai, K.K. Design, synthesis, in silico molecular docking and biological evaluation of novel oxadiazole based thiazolidine-2,4-diones bis-heterocycles as PPAR-γ agonists. Eur. J. Med. Chem., 2014, 87, 175-185.
[http://dx.doi.org/10.1016/j.ejmech.2014.09.010] [PMID: 25255433]
[25]
Yasmin, S.; Capone, F.; Laghezza, A.; Piaz, F.D.; Loiodice, F.; Vijayan, V.; Devadasan, V.; Mondal, S.K.; Atlı, Ö.; Baysal, M.; Pattnaik, A.K.; Jayaprakash, V.; Lavecchia, A. Novel benzylidene thiazolidinedione derivatives as partial PPARγ agonists and their antidiabetic effects on type 2 diabetes. Sci. Rep., 2017, 7(1), 14453.
[http://dx.doi.org/10.1038/s41598-017-14776-0] [PMID: 29089569]

Rights & Permissions Print Cite
Article Metrics
8
© 2024 Bentham Science Publishers | Privacy Policy