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Medicinal Chemistry Research

, Volume 27, Issue 2, pp 592–606 | Cite as

Imidazole-thiazole coupled derivatives as novel lanosterol 14-α demethylase inhibitors: ionic liquid mediated synthesis, biological evaluation and molecular docking study

  • Anna Pratima G. Nikalje
  • Shailee V. Tiwari
  • Aniket P. Sarkate
  • Kshipra S. Karnik
Original Research

Abstract

A novel series of imidazole-thiazole coupled derivatives (7a7q) were synthesized using Green protocol and identified by different spectroscopic techniques. The synthesized derivatives (7a7q) were evaluated for their in vitro antifungal activity against the six fungi strains. The compounds 7j and 7k exhibited the most promising antifungal activity. The compound 7k exhibited extremely high antifungal activity against C. albicans, C. glabrata, F. oxysporum, A. flavus, A. niger, and C. neoformans with MIC80 values of 0.2, 0.2, 20, 35, 40, and 5 µg/ml respectively. The mode of action of the most promising antifungal compounds 7j and 7k was established by ergosterol extraction and quantitation assay. From the ergosterol extraction and quantitation assay it was found that the compounds 7j and 7k act by inhibition of ergosterol biosynthesis in C. albicans. The molecular docking study revealed the high spontaneous binding ability of the tested compounds to the active site of lanosterol 14α-demethylase, which proves that the tested compounds inhibit the synthesis of lanosterol 14α-demethylase. The synthesized compounds were analyzed for ADMET properties to establish oral drug like behavior and shows satisfactory results. To establish the antifungal selectivity and safety, the most active compounds were further tested for cytotoxicity against human cancer cell lines HeLa and K-562 and were found to be non-cytotoxic in nature. The in vivo acute oral toxicity study was performed for the most active compounds and results indicate that the compounds are non-toxic in nature.

Keywords

Imidazole-thiazole Antifungal activity Ergosterol extraction and quantitation assay Molecular docking Acute oral toxicity 

Notes

Acknowledgements

The authors are thankful to Mrs. Fatima Zakaria, Chairman, Maulana Azad Educational Trust and Dr. Zahid Zaheer, Principal, Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431 001 (M.S.), India for providing the laboratory facility.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_2085_MOESM1_ESM.docx (1.7 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Anna Pratima G. Nikalje
    • 1
  • Shailee V. Tiwari
    • 1
  • Aniket P. Sarkate
    • 2
  • Kshipra S. Karnik
    • 2
  1. 1.Y. B. Chavan College of PharmacyDr. Rafiq Zakaria CampusAurangabadIndia
  2. 2.Department of Chemical TechnologyDr. Babasaheb Ambedkar Marathwada UniversityAurangabadIndia

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