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Synthesis of new 1,3,4-oxadiazole and benzothiazolylthioether derivatives of 4-arylmethylidene-3-substituted-isoxazol-5(4H)-one as potential antimycobacterial agents

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Abstract

A new series of 4-[(substituted benzylidene)-3-[(5-(pyridine-4-yl)-1,3,4-oxadiazole-2-ylthio)-methyl]isoxazol-5(4H)-one (6a–g) and 4-(substituted benzylidene)-3-((benzo[d]thiazol-2-ylthio)methyl)isoxazol-5(4H)-one (8a–g) was synthesized. All the synthesized compounds were screened for antitubercular activity against Mycobacterium tuberculosis H37Ra (ATCC 25177) and Mycobacterium bovis BCG (ATCC 35743) and antibacterial activity against Escherichia coli (NCIM 2576), Pseudomonas flurescence (NCIM 2059), Staphylococcus aureus (NCIM 2602), Bacillus subtilis (NCIM 2162). Amongst the synthesized 1,3,4-oxadiazole and benzothiazoyl thioether derivatives, compounds 6b and 8b showed excellent antimycobacterial activity and compounds 6b, 8a, 8b, and 8d showed excellent antibacterial activity against all tested antibacterial strains. The synthesized compounds were further evaluated for their cytotoxic activity against the HCT 116 and HeLa cancer cell lines. The 1,3,4-oxadiazole and benzothiazoyl thioether derivatives 6a–g and 8a–g did not show cytotoxicity.

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References

  • Abhale YK, Sasane AV, Chavan AP, Deshmukh KK, Kotapalli SS, Ummanni R, Sayyad SF, Mhaske PC (2015) Synthesis and biological screening of 2′-aryl/benzyl-2-aryl-4-methyl-4′,5-bithiazolyls as possible anti-tubercular and antimicrobial agents. Eur J Med Chem 94:340–347

    Article  CAS  Google Scholar 

  • Abhale YK, Sasane AV, Chavan AP, Shekh SH, Deshmukh KK, Bhansali S, Nawale L, Sarkar D, Mhaske PC (2017) Synthesis and antimycobacterial screening of new thiazolyl-oxazole derivatives. Eur J Med Chem 132:333–340

    Article  CAS  Google Scholar 

  • Achkar J, Fries B (2010) Candida infections of the genitourinary tract. Clin Microbiol Rev 23:253–273

    Article  Google Scholar 

  • Aminov R (2017) History of antimicrobial drug discovery: major classes and health impact. Biochem Pharm 133:4–19

    Article  CAS  Google Scholar 

  • Asan H, Sheikh M, Gapil S (2012) Synthesis, characterization and evaluation of some 5-substituted 1,3,4-oxadiazole-2-thioesters as antifungal agents. Asian J Chem 24:2573–2578

    Google Scholar 

  • Badrey M, Gomha S (2014) Synthesis and antibacterial activity of fused isoxazole derivatives using grinding method. Int J Pharm Pharm Sci 6:236–239

    CAS  Google Scholar 

  • Bradshaw T, Bibby M, Double J, Fichtner I, Cooper P, Alley M, Donohue S, Stinson S, Tomaszewjski J, Sausville E, Stevens M (2002) Preclinical evaluation of amino acid prodrugs of novel antitumor 2-(4-amino-3-methylphenyl)benzothiazoles. Mol Cancer Ther 1:239–246

    CAS  PubMed  Google Scholar 

  • Brown D, Wright D (2016) Antibacterial drug discovery in the resistance era. Nature 529:336–343

    Article  CAS  Google Scholar 

  • Cannon R, Lamping E, Holmes A, Niimi K, Baret P, Keniya M, Tanabe K, Niimi M, Goffeau A, Monk B (2009) Efflux-mediated antifungal drug resistance. Clin Microbiol Rev 22:291–321

    Article  CAS  Google Scholar 

  • Catriona G, Geoffrey W, Jean-Philippe C, Erica L, Bradshaw T, Malcolm F, Westwell A (2006) Antitumor benzothiazoles 2-(3,4-dimethoxyphenyl) fluorobenzothiazole (GW 610, NSC 721648), a simple fluorinated 2-arylbenzothiazole, shows potent and selective inhibitory activity against lung, colon and breast cancer cell lines. J Med Chem 49:179–185

    Article  Google Scholar 

  • Chavan A, Pinjari A, Mhaske P (2015) An efficient synthesis of 4-Arylmethylidene-3-substitutedisoxazol-5(4H)-ones in aqueous medium. J Heterocycl Chem 52:1911–1915

    Article  CAS  Google Scholar 

  • Chen H, Li Z, Han Y (2000) Synthesis and fungicidal activity against rhizoctoniasolani of 2-alkyl (alkylthio)-5-pyrazolyl-1,3,4-oxadiazoles (thiadiazoles). J Agric Food Chem 48:5312–5315

    Article  CAS  Google Scholar 

  • Choi K, Siegel M, Piper L, Yuan L, Cho E, Strnad P, Omary B, Rich M, Khosla C (2005) Chemistry and biology of dihydroisoxazole derivatives: selective inhibitors of human transglutaminase. Chem Biol 12:469–475

    Article  CAS  Google Scholar 

  • Coran A (2003) Chemistry of the vulcanization and protection of elastomers: a review of the achievements. J Appl Polym Sci 87:24–30

    Article  CAS  Google Scholar 

  • El-Hawash S, Soliman R, Youssef A, Ragab H, Elzahhar P, El-Ashmawey I, Abdel Wahab A, Shaat I (2014) Design, synthesis and biological screening of some pyridinylpyrazole and pyridinylisoxazole derivatives as potential anti-inflammatory, analgesic, antipyretic and antimicrobial agents. Med Chem 10:318–338

    Article  CAS  Google Scholar 

  • Gollapalli N (2015) Synthesis, characterization and antimicrobial evaluation of isoxazole derivatives. Der Pharma Chem 7:346–350

    Google Scholar 

  • Guo X, Ming Y, Zhao H, Hong K, Xing H, Yun Y (2014) Synthesis and bioactivities of novel 1,3,4-oxadiazole derivatives containing 1,2,3-thiadiazole moiety. Phosphorus Sulfur Silicon Relat Elem 189:1895–1900

    Article  Google Scholar 

  • Kathiravan M, Salake A, Chothe A, Dudhe P, Watode R, Mukta M, Gadhwe S (2012) The biology and chemistry of antifungal agents: a review. Bioorg Med Chem 20:5678–5698

    Article  CAS  Google Scholar 

  • Kaur H, Kumar S, Kumar A (2010) Synthesis, antipsychotic and anticonvulsant activity of some new pyrazolinyl/isoxazolinylindol-2-ones. Int J Chem Tech Res 2:1010–1019

    CAS  Google Scholar 

  • Khan A, Sarkar D (2008) A simple whole cell based high throughput screening protocol using Mycobacterium bovis BCG for inhibitors against dormant and active tubercle bacilli. J Microbiol Methods 73:62–68

    Article  CAS  Google Scholar 

  • Kim S, Christelle T, Peter V, Koen V, Hank K, Luc M, Guy B, Alfons V (2009) Synthesis and evaluation of 18F-labeled 2-phenylbenzothiazoles as positron emission tomography imaging agents for amyloid plaques in alzheimer’s disease. J Med Chem 52:1428–1437

    Article  Google Scholar 

  • Kozikowski A, Pieroni M, Lilienkampf A, Wan B, Wang Y, Franzblau S (2009) Synthesis, biological evaluation and structure-activity relationships for 5-[(E)-2-arylethenyl]-3-isoxazole carboxylic acid alkyl ester derivatives as valuable antitubercular chemotypes. J Med Chem 52:6287–6296

    Article  Google Scholar 

  • Kumar A, Maurya R, Sharma S, Ahmad P, Singh A, Tamrakar A, Srivastava A (2009) Design and synthesis of 3,5-diarylisoxazole derivatives as novel class of antihyperglycemic and lipid lowering agents. Bioorg Med Chem 17:5285–5292

    Article  CAS  Google Scholar 

  • Kunin C, Ellis W (2000) Antimicrobial activities of mefloquine and a series of related compounds. Antimicrob Agents Chemother 44:848–852

    Article  CAS  Google Scholar 

  • Li P, Yin J, Xu W, Wu J, He M, Hu D, Yang S, Song B (2013) Synthesis, antibacterial activities, and 3D-QSAR of sulfone derivatives containing 1, 3, 4-oxadiazole moiety. Chem Biol Drug Des 82:546–556

    Article  CAS  Google Scholar 

  • Li X, He D (2012) Synthesis, crystal structure and biological activity of 2-(anthracen-9-yl)-5-p-tolyl-1,3,4-oxadiazole. Chin J Struct Chem 31:367–372

    CAS  Google Scholar 

  • Liu Q, Hou X (2012) One-pot three-component synthesis of 3-methyl-4-arylmethylene- isoxazol-5(4H)-ones catalyzed by sodium sulfid. Phosphorus Sulfur Silicon Relat Elem 187:448–453

    Article  CAS  Google Scholar 

  • Mekuskiene G, Burbuliene M, JakubkieneV, Udrenaite E, Gaidelis P, Vainilavicius P (2003) 5-(4,6-Diphenyl-2-pyrimidinyl)-1,3,4-oxadiazole-2-thione with some C-electrophiles and N-nucleophiles. Chem Heterocycl Compd 39:1364–1368

    Article  CAS  Google Scholar 

  • Macaev F, Rusu G, Pogrebnoi S, Gudima A, Stingaci E, Vlad L, Shvets N, Kandemirli F, Dimoglo A, Reynolds R (2005) Synthesis of novel 5-aryl-2-thio-1,3,4-oxadiazoles and the study of their structure–anti-mycobacterial activities. Bioorg Med Chem 13:4842–4850

    Article  CAS  Google Scholar 

  • McReynolds M, Doughtery J, Hanson P (2004) Synthesis of phosphorus and sulfur heterocycles via ring-closing olefin metathesis. Chem Rev 104:2239–2258

    Article  CAS  Google Scholar 

  • Mondal P, Jana S, Balaji A, Ramakrishna R, Kantha L (2012) Synthesis of some new isoxazoline derivatives of chalconised indoline-2-one as a potential analgesic, antibacterial and anthelmimtic agents. J Young Pharmacol 4:38–41

    Article  CAS  Google Scholar 

  • Musser J, Brown R, Love B, Baily K, Jones H, Kahen R (1984) Synthesis of 2-(2,3-dihydro-2-oxo-l,3,4-oxadiazol-5-yl)benzoheterocycles a novel series of orally active antiallergic agents. J Med Chem 27:121–125

    Article  CAS  Google Scholar 

  • Muratov E, Varlamova E, Artemenko A, Khristova T, Kuz’min V, Makarov V, Riabova O, Wutzler P (2011) QSAR analysis of [(biphenyloxy)propyl] isoxazoles: agents against coxsackie virus B3. Future Med Chem 3:15–27

    Article  CAS  Google Scholar 

  • Powers J (2004) Antimicrobial drug development– the past, the present, and the future. Clin Micro Infec Dis 10:23–31

    Article  Google Scholar 

  • Quaglia W, Pigini M, Piergentili A, Giannella M, Gentili F, Marucci G, Carrieri A, Carotti A, Poggesi E, Leonardi A, Melchiorre C (2002) Structure−activity relationships in 1,4-benzodioxan-related compounds selectivity of 4-phenylchroman analogues for α1−adrenoreceptor subtypes. J Med Chem 45:1633–1643

    Article  CAS  Google Scholar 

  • Reddy C, Nagaraj A (2008) Synthesis of novel methylene-bis-isoxazoles as potential fungicidal agents. Heterocycl Commun 14:289–295

    CAS  Google Scholar 

  • Sahoo B, Dinda S, Kumar B, Panda J, Brahmkshatriya P (2014) Design, green synthesis, and anti-inflammatory activity of schiff base of 1,3,4-oxadiazoleanalogues. Lett Drug Des Disco 11:82–89

    Article  CAS  Google Scholar 

  • Sarkar S, Sarkar D (2012) Potential use of nitrate reductase as a biomarker for the identification of active and dormant inhibitors of Mycobacterium tuberculosis in a THP1 infection model. J Biomol Screen 7:966–973

    Article  Google Scholar 

  • Singh U, Akhtar S, Mishra A, Sarkar D (2011) A novel screening method based on menadione mediated rapid reduction of tetrazolium salt for testing of anti-mycobacterial agents. J Microbiol Methods 84:202–207

    Article  CAS  Google Scholar 

  • Srinivas A, Nagaraj A, Reddy C (2010) Synthesis and in vitro study of methylene-bistetrahydro[1,3]thiazolo[4,5-c]isoxazoles as potential nematicidal agents. Eur J Med Chem 45:2353–2358

    Article  CAS  Google Scholar 

  • Sugita Y, Hosoya H, Terasawa K, Yokoe I, Fujisawa S, Sakagami H (2001) Cytotoxic activity of benzothiepins against human oral tumor cell lines. Anticancer Res 21:2629–2632

    CAS  PubMed  Google Scholar 

  • SwissADME (2017) a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 7:42717

    Article  Google Scholar 

  • Tajik H, Dadras A (2011) Synthesis and herbicidal activity of novel 5-chloro-3-fluoro-2-phenoxypyridines with a 1,3,4-oxadiazole ring. J Pest Sci 36:27–32

    Article  CAS  Google Scholar 

  • Tatee T, Kurashige S, Shiozawa A, Narita K, Takei M (1986) Isoxazole derivatives as centrally acting muscle relaxants. I. Synthesis and activity of 5-(3-aminopropyl)amino-3- phenylisoxazole derivatives. Chem Pharm Bull 34:1634–1642

    Article  CAS  Google Scholar 

  • Wang Q, Sun R, Li Y, Xiong L, Liu Y (2011) Design, synthesis, and insecticidal evaluation of new benzoylureas containing isoxazoline and isoxazole group. J Agric Food Chem 59:4851–4859

    Article  Google Scholar 

  • Yong J, Lu C, Wu X (2014) Potential anticancer agents. I. Synthesis of isoxazole moiety containing quinazoline derivatives and preliminarily in vitro anticancer activity. Anticancer Agents Med Chem 15:131–136

    Article  Google Scholar 

  • Yoshida M, Hayakawa I, Hyashi N, Agatsuma T, Oda Y, Tanzawa F (2005) Synthesis and biological evaluation of benzothiazole derivatives as potent antitumor agents. Bioorg Med Chem Lett 15:3328–3332

    Article  CAS  Google Scholar 

  • Zhang C, Wang B, Liu X, Li Y, Wang S, Li Z (2008) Facile synthesis and herbicidal activities of new isoxazole derivatives via 1,3-dipolar cyclo addition reaction. Heterocycl Commun 14:397–404

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to express sincere thanks to Savitribai Phule Pune University, Pune and DST, New Delhi for providing financial assistance. CIF Savitribai Phule Pune University is also acknowledged for the spectral analysis.

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Authors and Affiliations

  1. Department of Chemistry, Sir Parashurambhau College, Affiliated to Savitribai Phule Pune University, Tilak Road, Pune, 411030, India

    Abhijit P. Chavan, Abhijit Shinde & Pravin C. Mhaske

  2. Department of Chemistry, HPT Arts and RYK Science College, Affiliated to Savitribai Phule Pune University, Nasik, 422005, India

    Abhijit P. Chavan & Vivek D. Bobade

  3. Department of Zoology, Modern College of Arts, Science and Commerce, Affiliated to Savitribai Phule Pune University, Shivajinagar Pune, Pune, 411005, India

    Rujuta R. Deshpande

  4. Department of Chemistry, Kirti M. Doongursee College, Affiliated to University of Mumbai, Kashinath Dhuru Road, Off. Veer Savarkar Marg, Dadar (W), Mumbai, 400028, India

    Nandkumar A. Borade

  5. CombiChemBio Resource Centre, CSIR-National Chemical Laboratory, Pune, 411008, India

    Dhiman Sarkar

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  1. Abhijit P. Chavan
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Correspondence to Pravin C. Mhaske or Vivek D. Bobade.

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Chavan, A.P., Deshpande, R.R., Borade, N.A. et al. Synthesis of new 1,3,4-oxadiazole and benzothiazolylthioether derivatives of 4-arylmethylidene-3-substituted-isoxazol-5(4H)-one as potential antimycobacterial agents. Med Chem Res 28, 1873–1884 (2019). https://doi.org/10.1007/s00044-019-02420-7

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