Synthesis and Docking Study of Novel 4-Thiazolidinone Derivatives as Anti-Gram-positive and Anti-H. pylori Agents

Author(s): Armin Khomami, Mohammadamin Rahimi, Arash Tabei, Parastoo Saniee, Arash Mahboubi, Alireza Foroumadi, Nasrin Nassiri Koopaei, Ali Almasirad*.

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 19 , Issue 3 , 2019

Submit Manuscript
Submit Proposal

Graphical Abstract:


Abstract:

Background: Bacterial resistance to the available antibiotics is a life threatening issue and researchers are trying to find new drugs to overcome this problem. Amongst the different structural classes, thiazolidinone-4-one, as a new effective pharmacophore against various bacteria, has been introduced.

Objective: A new series of 2-(5-(5-nitrothiophene-2-yl)-1,3,4-thiadiazole-2-ylimino)-5-arylidenethiazolidin- 4-one derivatives were designed and synthesized as new antibacterial agents.

Method: Target compounds were synthesized during 5 steps and their in vitro antibacterial and anti-H. pylori activities were evaluated. The interaction of the most active derivatives with the probable targets was assessed by Auto Dock 4.2 Program.

Results: The results showed that the most potent compounds, 18, 22 and 23, displayed antibacterial activity versus S.aureus, S.epidermidis, B.cereus and B.subtilis (MIC, 1.56-12.5 µg/mL) and none of the derivatives were active on tested Gram-negative bacteria. Compound 12 in all considered doses and compounds 10, and 27 had strong anti-H. pylori activity (inhibition zone >20 mm) in 25 μg disc. Docking studies determined suitable interactions and affinity of potent compounds with bacterial MUR B and H. pylori urease enzymes.

Conclusion: According to the results most of the derivatives are effective anti-bacterial agents and docking evaluation confirmed their possible mechanisms of actions as MURB and Urease inhibitors.

Keywords: Autodock 4.2, Gram-positive, H. pylori, MURB, Nitrothiophene, 1, 3, 4-Thiadiazole, Urease.

[1]
World Health Organization. The top ten causes of death., http://www.who.int/mediacentre/factsheets/fs310/en (October).
[2]
Leal, J.R.; Conly, J.; Henderson, E.A.; Manns, B.J. How externalities impact an evaluation of strategies to prevent antimicrobial resistance in health care organizations. Antimicrob. Resist. Infect. Control, 2017, 6(1), 53.
[3]
Icgen, B. VanA-Type MRSA (VRSA) Emerged in Surface Waters. Bull. Environ. Contam. Toxicol., 2016, 97(3), 359-366.
[4]
Saka, A.; Yagi, K.; Nimura, S. Endoscopic and histological features of gastric cancers after successful Helicobacter pylori eradication therapy. Gastric Cancer, 2016, 19(2), 524-530.
[5]
Whitener, C.J.; Park, S.Y.; Browne, F.A.; Parent, L.J.; Julian, K.; Bozdogan, B.; Appelbaum, P.C.; Chaitram, J.; Weigel, L.M.; Jernigan, J. Vancomycin-resistant Staphylococcus aureus in the absence of vancomycin exposure. Clin. Infect. Dis., 2004, 38(8), 1049-1055.
[6]
Hsiang, J.; Selvaratnam, S.; Taylor, S.; Yeoh, J.; Tan, Y.M.; Huang, J.; Patrick, A. Increasing primary antibiotic resistance and ethnic differences in eradication rates of Helicobacter pylori infection in New Zealand--a new look at an old enemy. N. Z. Med. J., 2013, 126, 64-76.
[7]
Hu, Y.; Li, C.Y.; Wang, X.M.; Yang, Y.H.; Zhu, H.L. 1,3,4-Thiadiazole: synthesis, reactions, and applications in medicinal, agricultural, and materials chemistry. Chem. Rev., 2014, 114(10), 5572-5610.
[8]
Talebi Bezmin Abadi, A.; Mobarez, A.M.; Taghvaei, T.; Wolfram, L. Antibiotic resistance of Helicobacter pylori in Mazandaran, North of Iran. Helicobacter, 2010, 15(6), 505-509.
[9]
Foroumadi, A.; Rineh, A.; Emami, S.; Siavoshi, F.; Massarrat, S.; Safari, F.; Rajabalian, S.; Falahati, M.; Lotfali, E.; Shafiee, A. Synthesis and anti-Helicobacter pylori activity of 5-(nitroaryl)-1,3,4-thiadiazoles with certain sulfur containing alkyl side chain. Bioorg. Med. Chem. Lett., 2008, 18(11), 3315-3320.
[10]
Mirzaei, J.; Siavoshi, F.; Emami, S.; Safari, F.; Khoshayand, M.R.; Shafiee, A.; Foroumadi, A. Synthesis and in vitro anti-Helicobacter pylori activity of N-[5-(5-nitro-2-heteroaryl)-1,3,4-thiadiazol-2-yl] thiomorpholines and related compounds. Eur. J. Med. Chem., 2008, 43(8), 1575-1580.
[11]
Foroumadi, A.; Asadipour, A.; Mirzaei, M.; Karimi, J.; Emami, S. Antituberculosis agents. V. Synthesis, evaluation of in vitro antituberculosis activity and cytotoxicity of some 2-(5-nitro-2-furyl)-1,3,4-thiadiazole derivatives. Il Farmaco, 2002, 57(9), 765-769.
[12]
Jain, A.K.; Sharma, S.; Vaidya, A.; Ravichandran, V.; Agrawal, R.K. 1,3,4‐thiadiazole and its derivatives: A review on recent progress in biological activities. Chem. Biol. Drug Des., 2013, 81(5), 557-576.
[13]
Hosseinzadeh, N.; Hasani, M.; Foroumadi, A.; Nadri, H.; Emami, S.; Samadi, N.; Faramarzi, M.A.; Saniee, P.; Siavoshi, F.; Abadian, N. 5-Nitro-heteroarylidene analogs of 2-thiazolylimino-4-thiazolidinones as a novel series of antibacterial agents. Med. Chem. Res., 2013, 22(5), 2293-2302.
[14]
Vicini, P.; Geronikaki, A.; Incerti, M.; Zani, F.; Dearden, J.; Hewitt, M. 2-Heteroarylimino-5-benzylidene-4-thiazolidinones analogues of 2-thiazolylimino-5-benzylidene-4-thiazolidinones with antimicrobial activity: Synthesis and structure-activity relationship. Bioorg. Med. Chem., 2008, 16(7), 3714-3724.
[15]
Tripathi, A.C.; Gupta, S.J.; Fatima, G.N.; Sonar, P.K.; Verma, A.; Saraf, S.K. 4-Thiazolidinones: The advances continue. Eur. J. Med. Chem., 2014, 72, 52-77.
[16]
Clinical and Laboratory Standards Institute (CLSI)Approved Standard Document. In M07-09, Reference method for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; clinical and laboratory standards institute; Wayne, PA, 2012.
[17]
Fang, Y.; Zhong, W.; Wang, Y.; Xun, T.; Lin, D.; Liu, W.; Wang, J.; Lv, L.; Liu, S.; He, J. Tuning the antimicrobial pharmacophore to enable discovery of short lipopeptides with multiple modes of action. Eur. J. Med. Chem., 2014, 83, 36-44.
[18]
Asadipour, A.; Edraki, N.; Nakhjiri, M.; Yahya-Meymandi, A.; Alipour, E.; Saniee, P.; Siavoshi, F.; Shafiee, A.; Foroumadi, A. Anti-Helicobacter pylori activity and Structure-Activity Relationship study of 2-Alkylthio-5-(nitroaryl)-1, 3, 4-thiadiazole Derivatives. Iran. J. Pharm. Res., 2013, 12(3), 281-287.
[19]
Foroumadi, A.; Safavi, M.; Emami, S.; Siavoshi, F.; Najjari, S.; Safari, F.; Shafiee, A. Structure-activity relationship study of a series of N-substituted piperazinyl-fluoroquinolones as anti-Helicobacter pylori agents. Med. Chem., 2008, 4(5), 498-502.
[20]
National committee for clinical laboratory standards. methods for antimicrobial susceptibility testing of anaerobic bacteria. Approved standard M11-A6. 6th ed. National Committee for Clinical Laboratory Standards, Villanova, A, USA, 2004.
[21]
Tavakolfar, S. Mousavi, E.; Almasirad, A.; Amanzadeh, A.; Mohamamd Atyabi, S.; Yaghamii, P.; Samiee-Sadr, S.; Salimi, M. In Vitro Anticancer effects of two new potent hydrazide compounds on leukemic cells Anti-Cancer Agent. Me.,, 2016, 16(12), 1646-1651.
[22]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791.
[23]
Ha, N.C.; Oh, S.T.; Sung, J.Y.; Cha, K.A.; Lee, M.H.; Oh, B.H. Supramolecular assembly and acid resistance of Helicobacter pylori urease. Nat. Struct. Mol. Biol., 2001, 8(6), 505-509.
[24]
Mansour, T.S.; Caufield, C.E.; Rasmussen, B.; Chopra, R.; Krishnamurthy, G.; Morris, K.M.; Svenson, K.; Bard, J.; Smeltzer, C.; Naughton, S. Naphthyl tetronic acids as multi‐target inhibitors of bacterial peptidoglycan biosynthesis. ChemMedChem, 2007, 2(10), 1414-1417.
[25]
ACD/ChemSketch Freeware.; 14.01. Advanced chemistry development, Inc: Toronto, On, Canada,. 2012.
[26]
Azizian, H.; Nabati, F.; Sharifi, A.; Siavoshi, F.; Mahdavi, M.; Amanlou, M. Large-scale virtual screening for the identification of new Helicobacter pylori urease inhibitor scaffolds. J. Mol. Model., 2012, 18(7), 2917-2927.


Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 19
ISSUE: 3
Year: 2019
Page: [239 - 249]
Pages: 11
DOI: 10.2174/1389557518666181017142630
Price: $58

Article Metrics

PDF: 16
HTML: 3