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. Issue 5 (26th April 2019)

• Record Type: Journal Article
• Authors: Shareef, Mohd Adil; Sirisha, K.; Khan, Irfan; Sayeed, Ibrahim Bin; Jadav, Surender Singh; Ramu, Gopathi; Kumar, C. Ganesh; Kamal, Ahmed; Babu, Bathini Nagendra
• Is Part Of: MedChemComm. Volume 10:Issue 5(2019)
• Page Start: 806
• Page End: 813
• Publication Date: 2019-04-26
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c9md00155g
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : Non-toxic compounds with antifungal activity, ergosterol inhibition and ROS inducing potential. 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. Compounds5d, 5g, 5j, 5k and5q demonstrated significant activity against the entire panel of test pathogens. Further, compounds5d and5g exhibited significant anti- Candida activity. These potential hybrids (5d and5g ) also exhibited promising ergosterol biosynthesis inhibition against Candida albicans, which was further validated through molecular docking studies. Furthermore, compounds5d and5g 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 that5d and5g may be considered as promising leads for further development of new antifungal drugs.