Carbonic anhydrase inhibitors(University of Wollongong)

In this study, a series of 6-ethoxyphenyl-4-fluorobenzenesulphonate-based thiosemicarbazones (5a-w) were synthesized via a two-step process and structurally characterized by ¹H NMR and ¹³C NMR spectroscopy. Their inhibitory activities against human carbonic anhydrase isoforms I and II (hCA I and hCA II) were evaluated, revealing potent inhibition at low nanomolar concentrations with IC₅₀ values ranging from 56.36 to 230.17 nM for hCA I and 30.66 to 175.45 nM for hCA II. Compounds 5a, 5g, and 5n exhibited the highest enzyme inhibition, with 5a identified as the most potent in vitro inhibitor for both isoforms. Molecular docking studies and MM-GBSA binding free energy calculations demonstrated that compound 5n displayed the strongest binding affinity toward hCA I, stabilized by key interactions including π-π stacking, hydrogen bonds, and coordination to the catalytic zinc ion. Molecular dynamics simulations over 100 ns confirmed the stability and dynamic adaptability of the 5n-hCA I and 5g-hCA II complexes, preserving critical interactions essential for binding. Validation of the docking protocol yielded RMSD values below 2.0 Å, supporting the reliability of the computational approach. Overall, these findings highlight compounds 5n and 5g as promising lead molecules for selective inhibition of hCA I and hCA II, with potential applications in the treatment of carbonic anhydrase-related disorders.

Presenting a case of peripapillary retinoschisis in a patient with glaucomatous optic neuropathy that resolved after changing therapy from topical bimatoprost to timolol/dorzolamide.

A 70-year-old female who presented for a second opinion for peripapillary retinoschisis in the left eye.

The patient’s visual acuity was 20/25 and 20/30 in the right and left eyes, respectively. Dilated fundoscopy revealed posterior vitreous detachment (PVD) of the left eye, temporal cupping with a superotemporal notch of the left optic nerve, and bilateral macular drusen and pigmentary changes of the retinal pigment epithelium (RPE). Optical coherence tomography of the macula of the left eye showed a PVD, drusen, and peripapillary retinoschisis extending to and involving the fovea. Topical prostaglandin analogue eye drop was discontinued and replaced by dorzolamide/timolol. The peripapillary retinoschisis resolved after medication change over the following 48 months and has not recurred.

We present a case of peripapillary retinoschisis in a phakic patient that developed during treatment with a topical prostaglandin analogue. The schisis resolved after switching the prostaglandin analogue to a topical carbonic anhydrase inhibitor. We suggest that the prostaglandin may have had a role in initiating peripapillary retinoschisis associated with glaucomatous optic neuropathy and that carbonic anhydrase inhibitors are a potential treatment for this condition.