Synthesis and evaluation of α-aminoacyl amides as antitubercular agents effective on drug resistant tuberculosis.

Amides / chemistry Animals Antitubercular Agents / chemistry Cell Line Chemistry, Pharmaceutical / methods Humans Microbial Sensitivity Tests Mycobacterium tuberculosis / drug effects Tuberculosis, Multidrug-Resistant / drug therapy
Antitubercular agents Drug-resistant tuberculosis Heterocyclic compounds Ugi reaction

Journal

European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510

Informations de publication

Date de publication:
15 Feb 2019
Historique:
received: 20 09 2018
revised: 30 12 2018
accepted: 01 01 2019
pubmed: 18 1 2019
medline: 7 3 2019
entrez: 18 1 2019
Statut: ppublish

Résumé

The development of an effective antitubercular agent is a challenge due to the complex nature of tuberculosis. Herein, we report the synthesis and evaluation of α-aminoacyl amides as antitubercular agents. The systematic medicinal chemistry approach led to identification of optimal substitutions required for the activity. Compound 11l was identified as antitubercular lead with drug like properties. Further, 11l selectively inhibited M. tuberculosis H37Rv with MIC value of 0.78 μM and was found to be non-toxic to CHOK1 cells. The lead compound inhibited multidrug resistant and Pre-Extensively drug resistant strains of Mycobacterium at 2 μg/mL and 8 μg/mL respectively.

Identifiants

DOI: 10.1016/j.ejmech.2019.01.002 PMID: 30654238
pubmed: 30654238
pii: S0223-5234(19)30002-9
doi: 10.1016/j.ejmech.2019.01.002
pii:
doi:

Substances chimiques

Amides 0
Antitubercular Agents 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

665-677

Informations de copyright

Copyright © 2019 Elsevier Masson SAS. All rights reserved.

Auteurs

Vitthal B Makane (VB)

Department of Organic Synthesis and Process Chemistry, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500 007, India; Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh, 201 002, India.

Vagolu Siva Krishna (VS)

Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet Mandal, R.R. District, Hyderabad, 500 078, India.

E Vamshi Krishna (EV)

Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh, 201 002, India; Department of Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500 007, India.

Manjulika Shukla (M)

Department of Microbiology, CSIR-Central Drug Research Institute, Lucknow, 226021, Uttar Pradesh, India.

B Mahizhaveni (B)

Department of Bacteriology, National Institute for Research in Tuberculosis, Chennai, India.

Sunil Misra (S)

Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh, 201 002, India; Department of Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500 007, India.

Sidharth Chopra (S)

Department of Microbiology, CSIR-Central Drug Research Institute, Lucknow, 226021, Uttar Pradesh, India.

Dharmarajan Sriram (D)

Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet Mandal, R.R. District, Hyderabad, 500 078, India.

V N Azger Dusthackeer (VNA)

Department of Bacteriology, National Institute for Research in Tuberculosis, Chennai, India.

Haridas B Rode (HB)

Department of Organic Synthesis and Process Chemistry, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500 007, India; Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh, 201 002, India. Electronic address: haridas.rode@iict.res.in.

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Classifications MeSH

questionsmedicales.fr › Composés chimiques organiques › Amides › Synthesis and evaluation of α-aminoacyl amides...
questionsmedicales.fr › Eucaryotes › Animaux › Synthesis and evaluation of α-aminoacyl amides...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antibactériens › Antituberculeux › Synthesis and evaluation of α-aminoacyl amides...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Synthesis and evaluation of α-aminoacyl amides...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Chimie pharmaceutique › Synthesis and evaluation of α-aminoacyl amides...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Synthesis and evaluation of α-aminoacyl amides...
questionsmedicales.fr › Techniques d'investigation › Évaluation préclinique de médicament › Tests de sensibilité microbienne › Synthesis and evaluation of α-aminoacyl amides...
questionsmedicales.fr › Bactéries › Bactéries à Gram positif › Bâtonnets à Gram positif › Bâtonnets asporogènes à Gram positif › Bâtonnets asporogènes réguliers à Gram positif › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis › Synthesis and evaluation of α-aminoacyl amides...
questionsmedicales.fr › Infection › Infections bactériennes et mycoses › Infections bactériennes › Infections bactériennes à Gram positif › Infections à Actinomycetales › Infections à Mycobacterium › Tuberculose › Tuberculose multirésistante › Synthesis and evaluation of α-aminoacyl amides...