Affiliations 

  • 1 Centre for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Malaysia
  • 2 Centre for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Malaysia; Volgograd State Medical University, Research Institute of Pharmacology, Volgograd, Russia. Electronic address: iezhitsa@salam.uitm.edu.my
  • 3 Volgograd State Medical University, Research Institute of Pharmacology, Volgograd, Russia
  • 4 Southern Federal University, Research Institute of Physical and Organic Chemistry, Rostov-on-Don, Russia
Eur J Pharm Sci, 2018 Mar 01;114:245-254.
PMID: 29274441 DOI: 10.1016/j.ejps.2017.12.015

Abstract

In an effort to find new ocular hypotensive drug candidates, a total of 27 condensed benzimidazoles based compounds were screened. This study was done in normotensive rats and rebound tonometry was used to estimate IOP. All compounds were topically applied as a single drop, unilaterally, at 3 different concentrations (0.1%, 0.2% and 0.4%). The contralateral eye was instilled with vehicle and served as control. The IOP reduction was measured up to 6h. It was observed that with a single topical instillation, compounds RU 551, RU 555, RU839 (pyrimido[1,2-a]benzimidazole derivatives), and RU 615 (imidazo[1,2-a]benzimidazole derivative) showed significant IOP lowering activities in ocular normotensive rats. All other compounds showed none, weak and inconsistent IOP lowering effect. The relationship between ability of IOP lowering and hypotensive activities was studied. According to the pharmacophore analysis, the class of pyrimido[1,2-a]benzimidazole is more promising than the class of imidazo[1,2-a]benzimidazole as a source of compounds with high IOP lowering activity. Pharmacophore analysis also showed that the critical features of high IOP lowering activity are methoxyphenyl and [phenyl]alkyl fragments, and non-conjugated six-membered heterocyclic ring.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.