FacIle syntheses and molecular-docking of novel substituted 3,4-dimethyl-1H-pyrrole-2-carboxamide/ carbohydrazide Analogues with antimicrobial and antifungal properties

Jitendra D. Bhosale, Rajesh Dabur, Gopal Jadhav, R. S. Bendre

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The article describes the use of facile one-pot, high-yielding reactions to synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamides 3a–m and carbohydrazide analogues 5a–l as potential antifungal and antimicrobial agents. The structural identity and purity of the synthesized compounds were assigned based on appropriate spectroscopic techniques. Synthesized compounds were assessed in vitro for antifungal and antibacterial activity. The compounds 5h, 5i and 5j were found to be the most potent against Aspergillus fumigatus, with MIC values of 0.039 mg/mL. The compound 5f bearing a 2, 6-dichloro group on the phenyl ring was found to be the most active broad spectrum antibacterial agent with a MIC value of 0.039 mg/mL. The mode of action of the most promising antifungal compounds (one representative from each series; 3j and 5h) was established by their molecular docking with the active site of sterol 14α-demethylase. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds in the access channel away from catalytic heme iron of the enzyme, which suggested that the tested compounds inhibit this enzyme and would avoid heme iron-related deleterious side effects observed with many existing antifungal compounds.

Original languageEnglish (US)
Article number875
JournalMolecules
Volume23
Issue number4
DOIs
StatePublished - Jan 1 2018

Fingerprint

Pyrroles
pyrroles
Heme
Sterol 14-Demethylase
enzymes
Bearings (structural)
Iron
analogs
Aspergillus
iron
Aspergillus fumigatus
Antifungal Agents
Enzymes
synthesis
Anti-Infective Agents
Catalytic Domain
purity
Anti-Bacterial Agents
rings
carbohydrazide

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

FacIle syntheses and molecular-docking of novel substituted 3,4-dimethyl-1H-pyrrole-2-carboxamide/ carbohydrazide Analogues with antimicrobial and antifungal properties. / Bhosale, Jitendra D.; Dabur, Rajesh; Jadhav, Gopal; Bendre, R. S.

In: Molecules, Vol. 23, No. 4, 875, 01.01.2018.

Research output: Contribution to journalArticle

@article{8dad9bb728d84f65a95429a187b17ca5,
title = "FacIle syntheses and molecular-docking of novel substituted 3,4-dimethyl-1H-pyrrole-2-carboxamide/ carbohydrazide Analogues with antimicrobial and antifungal properties",
abstract = "The article describes the use of facile one-pot, high-yielding reactions to synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamides 3a–m and carbohydrazide analogues 5a–l as potential antifungal and antimicrobial agents. The structural identity and purity of the synthesized compounds were assigned based on appropriate spectroscopic techniques. Synthesized compounds were assessed in vitro for antifungal and antibacterial activity. The compounds 5h, 5i and 5j were found to be the most potent against Aspergillus fumigatus, with MIC values of 0.039 mg/mL. The compound 5f bearing a 2, 6-dichloro group on the phenyl ring was found to be the most active broad spectrum antibacterial agent with a MIC value of 0.039 mg/mL. The mode of action of the most promising antifungal compounds (one representative from each series; 3j and 5h) was established by their molecular docking with the active site of sterol 14α-demethylase. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds in the access channel away from catalytic heme iron of the enzyme, which suggested that the tested compounds inhibit this enzyme and would avoid heme iron-related deleterious side effects observed with many existing antifungal compounds.",
author = "Bhosale, {Jitendra D.} and Rajesh Dabur and Gopal Jadhav and Bendre, {R. S.}",
year = "2018",
month = "1",
day = "1",
doi = "10.3390/molecules23040875",
language = "English (US)",
volume = "23",
journal = "Molecules",
issn = "1420-3049",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "4",

}

TY - JOUR

T1 - FacIle syntheses and molecular-docking of novel substituted 3,4-dimethyl-1H-pyrrole-2-carboxamide/ carbohydrazide Analogues with antimicrobial and antifungal properties

AU - Bhosale, Jitendra D.

AU - Dabur, Rajesh

AU - Jadhav, Gopal

AU - Bendre, R. S.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - The article describes the use of facile one-pot, high-yielding reactions to synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamides 3a–m and carbohydrazide analogues 5a–l as potential antifungal and antimicrobial agents. The structural identity and purity of the synthesized compounds were assigned based on appropriate spectroscopic techniques. Synthesized compounds were assessed in vitro for antifungal and antibacterial activity. The compounds 5h, 5i and 5j were found to be the most potent against Aspergillus fumigatus, with MIC values of 0.039 mg/mL. The compound 5f bearing a 2, 6-dichloro group on the phenyl ring was found to be the most active broad spectrum antibacterial agent with a MIC value of 0.039 mg/mL. The mode of action of the most promising antifungal compounds (one representative from each series; 3j and 5h) was established by their molecular docking with the active site of sterol 14α-demethylase. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds in the access channel away from catalytic heme iron of the enzyme, which suggested that the tested compounds inhibit this enzyme and would avoid heme iron-related deleterious side effects observed with many existing antifungal compounds.

AB - The article describes the use of facile one-pot, high-yielding reactions to synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamides 3a–m and carbohydrazide analogues 5a–l as potential antifungal and antimicrobial agents. The structural identity and purity of the synthesized compounds were assigned based on appropriate spectroscopic techniques. Synthesized compounds were assessed in vitro for antifungal and antibacterial activity. The compounds 5h, 5i and 5j were found to be the most potent against Aspergillus fumigatus, with MIC values of 0.039 mg/mL. The compound 5f bearing a 2, 6-dichloro group on the phenyl ring was found to be the most active broad spectrum antibacterial agent with a MIC value of 0.039 mg/mL. The mode of action of the most promising antifungal compounds (one representative from each series; 3j and 5h) was established by their molecular docking with the active site of sterol 14α-demethylase. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds in the access channel away from catalytic heme iron of the enzyme, which suggested that the tested compounds inhibit this enzyme and would avoid heme iron-related deleterious side effects observed with many existing antifungal compounds.

UR - http://www.scopus.com/inward/record.url?scp=85045267731&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045267731&partnerID=8YFLogxK

U2 - 10.3390/molecules23040875

DO - 10.3390/molecules23040875

M3 - Article

C2 - 29641457

AN - SCOPUS:85045267731

VL - 23

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 4

M1 - 875

ER -