Related Experiment Video

Updated: Jun 2, 2026

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones
07:30

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

Published on: January 21, 2020

Synthesis-guided design and discovery of alkylated indoles with antibacterial activity against MRSA

Auqib Rashid1,2,3, Vishwani Jamwal4,3, Bilal A Bhat2,3

  • 1Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine Jammu-180001 India showkatrashid.iiim@csir.res.in.

RSC Medicinal Chemistry
|June 1, 2026
PubMed

Insights

Antimicrobial resistance (AMR) is a global threat. Researchers developed novel indole derivatives, identifying potent compounds 14f and 14l effective against Methicillin-resistant Staphylococcus aureus (MRSA) infections.

Area of Science:

  • Medicinal Chemistry
  • Microbiology
  • Drug Discovery

Background:

  • Antimicrobial resistance (AMR) presents a critical global health challenge, leading to high morbidity and mortality.
  • Drug-resistant bacteria, particularly Methicillin-resistant Staphylococcus aureus (MRSA), necessitate urgent development of new therapeutic alternatives.
  • The diminishing pipeline of effective antibacterial drugs underscores the need for novel drug discovery strategies.

Purpose of the Study:

  • To design, synthesize, and evaluate novel C-3 alkylated indole derivatives as potential antibacterial agents.
  • To identify and optimize lead compounds with significant activity against MRSA.
  • To investigate the mechanism of action and safety profile of promising indole-based antibacterial candidates.

Main Methods:

  • Establishment of a synthetic and screening platform for indole derivative generation.
  • Biological assessment of synthesized compounds against MRSA, including determination of Minimum Inhibitory Concentration (MIC).
  • Structural modification of initial hits to create second-generation analogues for enhanced potency.
  • Evaluation of killing kinetics, anti-biofilm properties, cell integrity, membrane permeability, oxidative stress, and ATP depletion.

Main Results:

  • Initial screening identified hit molecules 9k and 11b with activity against MRSA.
  • Second-generation analogues led to potent compounds 14f and 14l (MICs 5.89 μM and 6.02 μM) against MRSA.
  • These potent hits demonstrated a favorable safety profile, effective killing kinetics, and anti-biofilm activity.
  • Compounds 14f and 14l were confirmed to target bacterial membranes, induce oxidative stress, and deplete ATP, leading to cell death.

Conclusions:

  • Novel indole-based scaffolds show promise as antibacterial agents against MRSA.
  • Compounds 14f and 14l represent promising lead candidates for further development.
  • The identified compounds exhibit a multi-faceted mechanism of action, including membrane disruption and induction of cellular stress.
  • This study provides a foundation for developing new indole-based therapeutics to combat MRSA infections.

More Related Videos

Visualization of Bacterial Resistance using Fluorescent Antibiotic Probes08:23

Visualization of Bacterial Resistance using Fluorescent Antibiotic Probes

Published on: March 2, 2020

Related Concept Videos

Antibiotic Selection00:57

Antibiotic Selection

Overview
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
Production of Antibiotics01:27

Production of Antibiotics

Penicillin, one of the earliest and most widely used antibiotics, is produced industrially by the filamentous fungus Penicillium chrysogenum. Large stirred-tank bioreactors ranging from tens to hundreds of thousands of liters maintain tightly controlled temperature, pH, and dissolved oxygen conditions to support fungal metabolism and maximize antibiotic yield. Penicillin is a secondary metabolite, synthesized primarily during the stationary growth phase, which requires a carefully managed...
Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...
Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...