Shareef Mohd Adil, Sirisha K, Khan Irfan, Sayeed Ibrahim Bin, Jadav Surender Singh, Ramu Gopathi, Kumar C Ganesh, Kamal Ahmed, Babu Bathini Nagendra
Department of Fluoro-Agrochemicals , CSIR-Indian Institute of Chemical Technology , Tarnaka , Hyderabad , India . Email:
Academy of Scientific and Innovative Research , New Delhi 110 025 , India.
Medchemcomm. 2019 Apr 26;10(5):806-813. doi: 10.1039/c9md00155g. eCollection 2019 May 1.
A series of new 1,4-dihydroindeno[1,2-]pyrazole tethered carbohydrazide hybrids () were designed, synthesized and evaluated for their antimicrobial activity. Compounds , , , and demonstrated significant activity against the entire panel of test pathogens. Further, compounds and exhibited significant anti- activity. These potential hybrids ( and ) also exhibited promising ergosterol biosynthesis inhibition against , which was further validated through molecular docking studies. Furthermore, compounds and caused intracellular ROS accumulation in MTCC 3017 and were non-toxic to normal human lung cell line MRC5. studies revealed that they demonstrated drug likeness and an appreciable pharmacokinetic profile. Overall, the findings demonstrate that and may be considered as promising leads for further development of new antifungal drugs.
设计、合成了一系列新型的1,4 - 二氢茚并[1,2 - ]吡唑连接的 carbohydrazide 杂化物(),并对其抗菌活性进行了评估。化合物、、、和对所有测试病原体均表现出显著活性。此外,化合物和表现出显著的抗活性。这些潜在的杂化物(和)对也表现出有前景的麦角固醇生物合成抑制作用,通过分子对接研究进一步得到验证。此外,化合物和在MTCC 3017中引起细胞内ROS积累,且对正常人肺细胞系MRC5无毒。研究表明它们具有药物相似性和可观的药代动力学特征。总体而言,研究结果表明和可被视为进一步开发新型抗真菌药物的有前景的先导化合物。