Synthesis of new 1,3,4-oxadiazole and benzothiazolylthioether derivatives of 4-arylmethylidene-3-substituted-isoxazol-5(4H)-one as potential antimycobacterial agents
- 5 Downloads
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.
KeywordsIsoxazol-5(4H)-one 1,3,4-Oxadiazole Benzothiazol Thioeteher Antitubercular activity Antibacterial activity
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 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 94:340–347Google 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 24:2573–2578Google Scholar
- Badrey M, Gomha S (2014) Synthesis and antibacterial activity of fused isoxazole derivatives using grinding method. Int J Pharm Pharm Sci 6:236–239Google 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 1:239–246Google 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 49:179–185CrossRefGoogle 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 10:318–338CrossRefGoogle Scholar
- Gollapalli N (2015) Synthesis, characterization and antimicrobial evaluation of isoxazole derivatives. Der Pharma Chem 7:346–350Google 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 2:1010–1019Google 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 52:6287–6296CrossRefGoogle 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 31:367–372Google 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 45:1633–1643CrossRefGoogle Scholar
- Reddy C, Nagaraj A (2008) Synthesis of novel methylene-bis-isoxazoles as potential fungicidal agents. Heterocycl Commun 14:289–295Google 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 21:2629–2632Google Scholar