Symmetric molecules with 1,4-triazole moieties as potent inhibitors of tumour-associated lactate dehydrogenase-A

Abdul-Malek S Altamimi; Ahmed M Alafeefy; Agnese Balode; Igor Vozny; Aleksandrs Pustenko; Mohey Eldin El Shikh; Fatmah A S Alasmary; Sherif A Abdel-Gawad; Raivis Žalubovskis

doi:10.1080/14756366.2017.1404593

Symmetric molecules with 1,4-triazole moieties as potent inhibitors of tumour-associated lactate dehydrogenase-A

J Enzyme Inhib Med Chem. 2018 Dec;33(1):147-150. doi: 10.1080/14756366.2017.1404593.

Authors

Affiliations

¹ a Department of Pharmaceutical Chemistry, College of Pharmacy , Prince Sattam Bin Abdulaziz University , Alkharj , Saudi Arabia.
² b Department of Chemistry , Kulliyyah of Science, International Islamic University Malaysia.
³ c Latvian Institute of Organic Synthesis , Riga , Latvia.
⁴ d Institute of Technology of Organic Chemistry, Faculty of Materials Science and Applied Chemistry , Riga Technical University , Riga , Latvia.
⁵ e Experimental Medicine and Rheumatology , William Harvey Research Institute, Queen Mary University of London , London , UK.
⁶ f Chemistry Department, College of Science , King Saud University , Saudi Arabia , Riyadh.
⁷ g Analytical Chemistry Department, Faculty of Pharmacy , Cairo University , Cairo , Egypt.

Abstract

A series of symmetric molecules incorporating aryl or pyridyl moieties as central core and 1,4-substituted triazoles as a side bridge was synthesised. The new compounds were investigated as lactate dehydro-genase (LDH, EC 1.1.1.27) inhibitors. The cancer associated LDHA isoform was inhibited with IC₅₀ = 117-174 µM. Seven compounds exhibited better LDHA inhibition (IC₅₀ 117-136 µM) compared to known LDH inhibitor - galloflavin (IC₅₀ 157 µM).

Keywords: Lactate dehydrogenase; inhibitors; triazole.

MeSH terms

Dose-Response Relationship, Drug
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Isocoumarins / chemistry
Isocoumarins / pharmacology*
L-Lactate Dehydrogenase / antagonists & inhibitors*
L-Lactate Dehydrogenase / metabolism
Molecular Structure
Structure-Activity Relationship
Triazoles / chemistry
Triazoles / pharmacology*

Substances

Enzyme Inhibitors
Isocoumarins
Triazoles
galloflavin
L-Lactate Dehydrogenase

Grants and funding

This project was supported by the National Plan of Science, Technology and Innovation [Grant No. 12-MED2980–54], Prince Sattam bin Abdulaziz University, Alkharj, PO Box 173, 11942.