Related Experiment Video

Updated: May 21, 2026

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)

Published on: January 20, 2016

From multiply active natural product to candidate drug? Antibacterial (and other) minor groove binders for DNA

Colin Suckling¹

¹WestCHEM, Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, UK. c.j.suckling@strath.ac.uk

Future Medicinal Chemistry

|June 2, 2012

Abstract:

Natural products that bind to DNA in the minor groove are valuable templates for drug design. Examples include distamycin, netropsin, duocarmycin and anthramycin. Anticancer and anti-infective drugs feature strongly amongst their derivatives. The structures and activities of chemotypes with various therapeutic actions are discussed in the context of the broader field of therapeutically active minor groove binders. The evolution of a series of exceptionally potent and nontoxic antibacterial compounds is discussed using the general design principle of introducing additional hydrophobicity into the distamycin template to increase the strength of binding to DNA. As well as potent antibacterial compounds, antifungal and antiparasitic compounds with exceptional cellular activity against trypanosomes have been identified. Possible mechanisms of action including gene regulation and topoisomerase inhibition are discussed with the need in mind to understand selective toxicity in the series to support future drug discovery.

More Related Videos

Mapping the Binding Site of an Aptamer on ATP Using MicroScale Thermophoresis

Mapping the Binding Site of an Aptamer on ATP Using MicroScale Thermophoresis

Published on: January 7, 2017

Assay Development for High-Throughput Drug Screening Against Mycobacteria

Assay Development for High-Throughput Drug Screening Against Mycobacteria

Published on: October 25, 2024

Related Concept Videos

Inhibitors of Bacterial DNA Synthesis

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...

Single-Strand DNA Binding Proteins

Single-Strand DNA Binding Proteins

For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...

Targets for Drug Action: Overview

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...

Inhibitors of Bacterial Protein Synthesis

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...

Inhibitors of Gram-positive Cell Wall Synthesis

Inhibitors of Gram-positive Cell Wall Synthesis

Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...

DNA Base Pairing

DNA Base Pairing

Erwin Chargaff’s rules on DNA equivalence paved the way for the discovery of base pairing in DNA. Chargaff’s rules state that in a double-stranded DNA molecule,

Articles linked to this work by shared authors, journal, and citation graph.

Carbazole derivatives as privileged scaffolds for kinase inhibition: advances in design, therapeutic applications and mechanisms.

Future medicinal chemistry·2026

Investigating the effect of glucosamine conjugation on the inhibitory ‎activity of 2,3-dihydro-1H-perimidine derivatives against protein tyrosine ‎phosphatases.

Future medicinal chemistry·2026

α‑Aminophosphonates in anticancer drug discovery: synthetic strategies, anticancer activities, structure-activity relationships and molecular mechanisms.

Future medicinal chemistry·2026

New hybrid molecules with 2,3,4,9-tetrahydro-1H-carbazol-1,3,4-oxadiazole-N-phenylacetamide framework as potent cholinesterase inhibitors.

Future medicinal chemistry·2026

Therapeutic prospects of thiazolo[3,2-b][1,2,4]triazole derivatives: a comprehensive review of biological activities and structure-activity relationship insights.

Future medicinal chemistry·2026

Integrated machine learning, pharmacophore screening, and structure-based computational approaches for the identification of novel JAK3 inhibitors.

Future medicinal chemistry·2026

See all related articles