2. Academic Validation
  3. Design, synthesis, and antimicrobial evaluation of 1,4-dihydroindeno[1,2- c]pyrazole tethered carbohydrazide hybrids: exploring their in silico ADMET, ergosterol inhibition and ROS inducing potential

Design, synthesis, and antimicrobial evaluation of 1,4-dihydroindeno[1,2- c]pyrazole tethered carbohydrazide hybrids: exploring their in silico ADMET, ergosterol inhibition and ROS inducing potential

  • Medchemcomm. 2019 Apr 26;10(5):806-813. doi: 10.1039/c9md00155g.
Mohd Adil Shareef 1 2,  K Sirisha 2 3,  Irfan Khan 2 3,  Ibrahim Bin Sayeed 2 3,  Surender Singh Jadav 1,  Gopathi Ramu 1 2,  C Ganesh Kumar 3,  Ahmed Kamal 4,  Bathini Nagendra Babu 1 2
Affiliations

Affiliations

  • 1 Department of Fluoro-Agrochemicals , CSIR-Indian Institute of Chemical Technology , Tarnaka , Hyderabad , India . Email: bathini@iict.res.in.
  • 2 Academy of Scientific and Innovative Research , New Delhi 110 025 , India.
  • 3 Organic Synthesis and Process Chemistry Division , CSIR-Indian Institute of Chemical Technology , Tarnaka , Hyderabad 500007 , India.
  • 4 School of Pharmaceutical Education and Research , Jamia Hamdard University , New Delhi 110062 , India . Email: ahmedkamal915@gmail.com.
PMID: 31191871 DOI: 10.1039/c9md00155g
Abstract

A series of new 1,4-dihydroindeno[1,2-c]pyrazole tethered carbohydrazide hybrids (5a-u) were designed, synthesized and evaluated for their antimicrobial activity. Compounds 5d, 5g, 5j, 5k and 5q demonstrated significant activity against the entire panel of test pathogens. Further, compounds 5d and 5g exhibited significant anti-Candida activity. These potential hybrids (5d and 5g) also exhibited promising ergosterol biosynthesis inhibition against Candida albicans, which was further validated through molecular docking studies. Furthermore, compounds 5d and 5g caused intracellular ROS accumulation in C. albicans MTCC 3017 and were non-toxic to normal human lung cell line MRC5. In silico studies revealed that they demonstrated drug likeness and an appreciable pharmacokinetic profile. Overall, the findings demonstrate that 5d and 5g may be considered as promising leads for further development of new Antifungal drugs.

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