Related Experiment Video

Updated: Aug 6, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
11:51

Facile Preparation of 4-Substituted Quinazoline Derivatives

Published on: February 15, 2016

1-Aryl-6,7-Dimethoxy-3,4-Dihydroisoquinoline-2(1H)-Sulfonamides as hCA XII Selective Inhibitors: Experimental and

Federico Ricci1, Anna Di Fiore2, Andrea Angeli3

  • 1CHIBIOFARAM Department, University of Messina, Messina, Italy.

Chemmedchem
|July 23, 2026
PubMed

Insights

Researchers developed novel carbonic anhydrase inhibitors (hCAIs) targeting human carbonic anhydrase XII (hCA XII), a key player in cancer progression. These potent and selective hCA XII inhibitors offer a promising avenue for developing new cancer therapies with fewer side effects.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Oncology

Background:

  • Human carbonic anhydrase XII (hCA XII) is a significant pharmacological target in cancer.
  • hCA XII regulates pH, impacting cancer cell proliferation, invasion, growth, and metastasis.
  • Developing selective hCA inhibitors (hCAIs) is challenging due to isoform similarity.

Purpose of the Study:

  • To evaluate a series of novel 1-aryl-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-sulfonamides for their inhibitory effects on hCA XII.
  • To assess the isoform selectivity of these compounds compared to existing inhibitors.
  • To elucidate the molecular basis for selective hCA XII inhibition.

Main Methods:

  • In vitro enzyme inhibition assays to determine inhibitory constants (Ki).
  • Isoform selectivity profiling against various carbonic anhydrase enzymes.
  • X-ray crystallography and computational modeling to understand binding interactions.

Main Results:

  • Three novel compounds demonstrated potent inhibition of hCA XII at low nanomolar concentrations (Ki 5.5–6.5 nM).
  • These compounds exhibited remarkable selectivity for hCA XII over other isoforms, outperforming the clinical candidate SLC-0111.
  • Structural analyses revealed key molecular interactions responsible for the observed selectivity.

Conclusions:

  • The identified 1-aryl-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-sulfonamides are potent and selective hCA XII inhibitors.
  • These findings provide a strong foundation for the rational design of targeted hCA XII-based cancer therapeutics.
  • The developed inhibitors offer a promising alternative for cancer treatment with potentially reduced off-target effects.
Keywords:
cancercarbonic anhydrasechemistrycrystallographydocking (molecular)drug designextracellularmedicinal chemistryrational design

More Related Videos

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

Related Concept Videos

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...
Amines to Sulfonamides: The Hinsberg Test01:23

Amines to Sulfonamides: The Hinsberg Test

The Hinsberg test is a method to identify primary, secondary and tertiary amines, named after its pioneer, Oscar Hinsberg. Here, amines are treated with benzenesulfonyl chloride, also known as the Hinsberg reagent, in the presence of an excess of aqueous base, followed by acidification. Based on the nature of the amines, different changes are observed.
Generally, a primary amine reacts with the Hinsberg reagent to produce an N-substituted benzenesulfonamide. The electron-withdrawing sulfonyl...
Stereoisomerism of Cyclic Compounds02:33

Stereoisomerism of Cyclic Compounds

In this lesson, we delve into the role of ring conformation and its stability, which determines the spatial arrangement and, consequently, the molecular symmetry and stereoisomerism of cyclic compounds. 1,2-Dimethylcyclohexane is used as a case study to evaluate the possible number of stereoisomers. Here, given the multiple (n = 2) chiral centers, there are 2n = 4 possible configurations that lack a plane of symmetry, as the ring skeleton exists in a non-planar chair conformation. In addition,...
Disubstituted Cyclohexanes: cis-trans Isomerism02:37

Disubstituted Cyclohexanes: cis-trans Isomerism

Depending upon the different spatial orientation of the substituents, the disubstituted cycloalkanes exhibit two types of stereoisomers. The cis isomers have the substituents on the same side of the ring, whereas the trans isomers have the substituents on the opposite sides. These stereoisomers exhibit different physical properties and cannot be interconverted without breaking the carbon-carbon bonds.
In cyclohexane, the substituents can occupy different positions generating distinct isomers.
Antifungal Agents01:15

Antifungal Agents

Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...