The effect of synthesized 5-R-1H-benzo[d]imidazole-2-thiol derivatives on intraocular pressure in normal and pathological conditions
Authors
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Alena S. Taran
Volgograd State Medical University
https://orcid.org/0000-0001-8477-254X
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Olga N. Zhukovskaya
Institute of Physical and Organic Chemistry of the Southern Federal University
https://orcid.org/0000-0003-2485-2139
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Lyudmila V. Naumenko
Volgograd State Medical University
https://orcid.org/0000-0002-2119-4233
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Alina M. Chebanko
Volgograd State Medical University
https://orcid.org/0009-0004-3140-5040
- Yuliya V. Efremova Volgograd State Medical University
- Irina D. Bodrug Volgograd State Medical University
- Anna А. Beloshapka Federal State Budgetary Educational Institution of the Volgograd State Medical University of the Ministry of Health of Russia, Volgograd
- Svetlana B. Zaichenko Institute of Physical and Organic Chemistry of the Southern Federal University
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Anatoly S. Morkovnik
Institute of Physical and Organic Chemistry
https://orcid.org/0000-0002-9182-6101
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Alexander A. Spasov
Volgograd State Medical University
https://orcid.org/0000-0002-7185-4826
DOI:
https://doi.org/10.18413/rrpharmacology.11.570Abstract
and do not have a resorptive effect is a topical task for the treatment of glaucoma. Eighteen derivatives of 5-R-1H-benzo[d]imidazole-2-thiols were synthesized and studied for ophthalmic hypotensive activity in animals with normal intraocular pressure and in animals with dexamethasone-induced ophthalmic hypertension.
Materials and Methods: Ophthalmohypotensive activity was studied by tonometry with the TonoVet veterinary tonometer in 90 intact and experimental sexually mature mongrel rats weighing 250-350g before and after instillation of solutions of the studied compounds. Local irritant effects were determined by performing a conjunctival test using 25 guinea pigs.
Results: The most active compound among the 5-R-1H-benzo[d]imidazole-2-thiol derivatives was compound 1a, which reduced the ophthalmotonus in normotensive animals by 31.37%, exceeding the effect of the reference drugs timolol (-26.84%) and melatonin (-30.95%), and in rats with dexamethasone-induced glaucoma – by 23.74%, similar to melatonin (-23.72%), but inferior to timolol (-29.75%). It was found that substance 1a has no local irritant effect. It was revealed that at the screening concentration (4 mg/mL), compound 1a has a systemic effect, at lower concentrations, the ophthalmohypotensive effect decreases, the latent period increases, and the severity of the resorptive effect decreases.
Conclusion: The most active compound, 1a, was found to have demonstrated in vivo IOP-lowering activity when administered as a single instillation at a concentration of 0.4% (4 mg/mL) in ophthalmonormotensive animals and animals with steroid-induced glaucoma. Compound 1a was shown to have no local irritant effect.
Graphical Abstract
Keywords:
glaucoma, intraocular pressure, benzimidazole, melatoninReferences
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Copyright (c) 2025 Taran AS, Zhukovskaya ON, Naumenko LV, Chebanko AM, Efremova YuV, Bodrug ID, Beloshapka AA, Zaichenko SB, Morkovnik AS, Spasov AA
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