Medicinal Chemistry Research

, Volume 26, Issue 11, pp 2889–2899 | Cite as

Synthesis, antimycobacterial screening and molecular docking studies of 4-aryl-4′-methyl-2′-aryl-2,5′-bisthiazole derivatives

  • Yogita K. Abhale
  • Abhijit D. Shinde
  • Keshav K. Deshmukh
  • Laxman Nawale
  • Dhiman Sarkar
  • Prafulla B. Choudhari
  • Santosh S. Kumbhar
  • Pravin C. MhaskeEmail author
Original Research


A series of 4-aryl-4′-methyl-2′-aryl-2,5′-bisthiazole derivatives (5ao) were synthesized and screened for inhibitory activity against Mycobacterium tuberculosis H37Ra (ATCC 25177) and Mycobacterium bovis BCG (ATCC 35743) strains. Five lead compounds (5e, 5f, 5g, 5h, and 5o) were further confirmed from their dose dependent effect against MTB and Bovine–Calmette–Guerin. The most promising compounds 5f (MIC90: 11.32 µg/mL), 5h (MIC90: 11.59 µg/mL), and 5o (MIC90: 23.64 µg/mL) showed strong antitubercular activity against dormant MTB and BCG as well as almost insignificant cytotoxicity up to 100 µg/mL against HeLa, A549, and PANC-1 human cancer cell lines. Further, the synthesized compounds were found to have potential antibacterial activity against Gram-negative bacteria, Escherichia coli, Pseudomonas flurescence and Gram-positive bacteria, Staphylococcus aureus, Bacillus subtilis. Most of the synthesized compounds showed moderate activity against fungal strain Candida albicans. Molecular docking studies of these compounds showed significant interactions with crystal structure of the cytochrome P45014α-sterol demethylase (CYP51) PDB ID: 1E9X. Hydrogen bond interactions with SER261 and VAL395 are important interactions for selective inhibition of designed inhibitors. Compounds 5f, 5h, and 5o showed significant interactions with 1E9X. All the experimental results promote us to consider this series as a starting point for the development of novel, selective and more potent antitubercular agents in the future.


Bisthiazoles Mycobacterium tuberculosis Antimicrobial activity Cytotoxicity Docking study 



YKA expresses her gratefulness to CSIR [File No. 08/590(0001)/2012-EMR-I] for the financial support. PCM would like to thank University Grant Commission (UGC No. 42-355(SR)/2013), New Delhi, India for the financial assistance and CSIR-NCL, Pune for supporting biological activity. Central Analysis facility, Savitribai Phule Pune University, Pune is also acknowledged for spectral analysis.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_1988_MOESM1_ESM.docx (635 kb)
Supplementary Information


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Yogita K. Abhale
    • 1
  • Abhijit D. Shinde
    • 2
  • Keshav K. Deshmukh
    • 1
  • Laxman Nawale
    • 3
  • Dhiman Sarkar
    • 3
  • Prafulla B. Choudhari
    • 4
  • Santosh S. Kumbhar
    • 4
  • Pravin C. Mhaske
    • 2
    Email author
  1. 1.Post-Graduate Department of Chemistry and Research Centre, S. N. Arts, D. J. M. Commerce and B. N. S. Science CollegeSavitribai Phule Pune UniversitySangamnerIndia
  2. 2.Post Graduate Department of Chemistry, S. P. Mandali’s Sir Parashurambhau CollegeSavitribai Phule Pune UniversityPuneIndia
  3. 3.CombiChemBio Resource Centre, CSIR-National Chemical LaboratoryPuneIndia
  4. 4.Department of Pharmaceutical ChemistryBharati Vidyapeeth College of PharmacyKolhapurIndia

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