Hidden targets in dermatology: In vitro and In silico inhibitory effects of common 23 dermatologic drugs on human carbonic anhydrase isoenzymes I and II.

Abstract

In this study, we have aimed to determine the in vitro and in silico effects of 23 frequently used dermatologic drugs on human carbonic anhydrase I (hCA I) and II (hCA II). The inhibitory effects of the drugs on hCA I and hCA II were determined by esterase methods. The most potent inhibitors were isotretinoin for hCA I (Ki= 5.75 µM) and valaciclovir for hCA II (Ki= 5.74 µM). Ketotifen (Ki= 6.98 µM), pantoprazole (Ki= 7.16 µM) and acyclovir (Ki= 7.31 µM) were also potent inhibitors for hCA I. Isotretinoin (Ki= 6.54 µM), brivudine (Ki= 7.44 µM) and fluconazole (Ki= 7.91 µM) were also potent inhibitors for hCA II. Terbinafine hydrochloride was a weak CA inhibitor for both of these isoenzymes (Ki= 20.58 µM for hCA I and 20.32 µM for hCA I). Therefore, the drug, having a weak CA inhibitory activity, may be preferred primarily in patients with a skin disease compared to the other drugs due to important physiological functions of CAs. Molecular docking studies have shown that acitretin and isotretinoin, in particular, will inhibit hCA I at lower concentrations and have higher docking scores. For hCA II, it was shown that Isotretinoin and Ketotifen would inhibit at lower concentrations and have higher placement scores.