Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2- a ]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies.

Autor: Venugopala KN; Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.; Department of Biotechnology and Food Technology, Durban University of Technology, Durban 4001, South Africa., Uppar V; Department of Chemistry, School of Basic Science, Rani Channamma University, Belagavi 591156, India., Chandrashekharappa S; Institute for Stem Cell Biology and Regenerative Medicine, National Center for Biological Sciences (NCBS), Tata Institute of Fundamental Research (TIFR), Gandhi Krishi Vignana Kendra (GKVK) Campus, Bangalore 560065, India., Abdallah HH; Chemistry Department, College of Education, Salahaddin University, Erbil 44001, Iraq., Pillay M; Department of Microbiology, National Health Laboratory Services, KZN Academic Complex, Inkosi Albert Luthuli Central Hospital, Durban 4001, South Africa., Deb PK; Faculty of Pharmacy, Philadelphia University, Amman 19392, Jordan., Morsy MA; Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.; Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt., Aldhubiab BE; Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia., Attimarad M; Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia., Nair AB; Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia., Sreeharsha N; Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia., Tratrat C; Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia., Yousef Jaber A; Faculty of Pharmacy, Philadelphia University, Amman 19392, Jordan., Venugopala R; Department of Public Health Medicine, University of KwaZulu-Natal, Howard College Campus, Durban 4001, South Africa., Mailavaram RP; Department of Pharmaceutical Chemistry, Shri Vishnu College of Pharmacy, Vishnupur, Bhimavaram 534 202, India., Al-Jaidi BA; Faculty of Pharmacy, Yarmouk University, Irbid 21163, Jordan., Kandeel M; Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia.; Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt., Haroun M; Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia., Padmashali B; Department of Chemistry, School of Basic Science, Rani Channamma University, Belagavi 591156, India.
Jazyk: angličtina
Zdroj: Antibiotics (Basel, Switzerland) [Antibiotics (Basel)] 2020 May 07; Vol. 9 (5). Date of Electronic Publication: 2020 May 07.
DOI: 10.3390/antibiotics9050233
Abstrakt: A series of ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2- a ]quinoline-3-carboxylates 4a - f and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2- a ]quinoline-2,3-dicarboxylates 4g - k have been synthesized and evaluated for their anti-tubercular (TB) activities against H37Rv (American Type Culture Collection (ATCC) strain 25177) and multidrug-resistant (MDR) strains of Mycobacterium tuberculosis by resazurin microplate assay (REMA). Molecular target identification for these compounds was also carried out by a computational approach. All test compounds exhibited anti-tuberculosis (TB) activity in the range of 8-128 µg/mL against H37Rv. The test compound dimethyl-1-(4-fluorobenzoyl)-5-methylpyrrolo[1,2- a ]quinoline-2,3-dicarboxylate 4j emerged as the most promising anti-TB agent against H37Rv and multidrug-resistant strains of Mycobacterium tuberculosis at 8 and 16 µg/mL, respectively. In silico evaluation of pharmacokinetic properties indicated overall drug-likeness for most of the compounds. Docking studies were also carried out to investigate the binding affinities as well as interactions of these compounds with the target proteins.
Databáze: MEDLINE