Intraocular pressure lowering effect and structure-activity relationship of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole compounds in ocular normotensive rats: Insight on possible link with hypotensive activity
Autor: | Bushra Johari, Igor Nikolayevich Iezhitsa, Alexander A. Spasov, O. N. Zhukovskaya, V. A. Anisimova, Pavel M. Vassiliev, Nafeeza Mohd Ismail, Adrian Julian Marcus, Renu Agarwal |
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Rok vydání: | 2017 |
Předmět: |
Benzimidazole
Intraocular pressure genetic structures Hypotensive drug Pharmaceutical Science Administration Ophthalmic Pharmacology 01 natural sciences Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship 0302 clinical medicine Structure–activity relationship Animals Antihypertensive Agents Intraocular Pressure Chemistry REBOUND TONOMETRY eye diseases 0104 chemical sciences Rats 010404 medicinal & biomolecular chemistry Treatment Outcome 030221 ophthalmology & optometry Benzimidazoles sense organs Pharmacophore Benzimidazole derivative |
Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 114 |
ISSN: | 1879-0720 |
Popis: | 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. |
Databáze: | OpenAIRE |
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