Emine Salamci

Carbonic anhydrase inhibitors: inhibition of human and bovine isoenzymes by benzenesulphonamides, cyclitols and phenolic compounds

Carbonic anhydrase inhibitors (CAIs) are a class of pharmaceuticals used as anti-glaucoma agents, diuretics and anti-epileptics. We report here the inhibitory capacities of benzenesulphonamides, cyclitols and phenolic compounds 1–11 against three human CA isozymes (hCA I, hCA II and hCA VI) and bovine skeletal muscle carbonic anhydrase III (bCA III). The four isozymes showed quite diverse inhibition profiles with Ki values ranging from low micromolar to millimolar concentrations against all isoenzymes. Compound 5 and 6 had more powerful inhibitory action against hCA I and very similar action against hCA II and hCA VI as compared with acetazolamide (AZA) and sulphapyridine (SPD), specific CAIs. Probably the inhibition mechanism of the tested compounds is distinct of the sulphonamides with RSO2NH2 groups and similar to that of the coumarins/lacosamide, i.e. binding to a distinct part of the active site than that where sulphonamides bind. These data may lead to drug design campaigns of effective CAIs possessing a diverse inhibition mechanism compared to other sulphonamide/sulphamate inhibitors.

A novel and short synthesis of (1,4/2)-cyclohex-5-ene-triol and its conversion to (±)-proto-quercitol

(1,4/2)-cyclohex-5-ene-triol was synthesized starting from cyclohexa-1,4-diene with two different approaches. Photooxygenation of cyclohexa-1,4-diene and epoxy-cyclohexene afforded anti-2,3-dioxabicyclo[2.2.2]oct-7-en-5-yl hydroperoxide and anti-7-oxabicyclo[4.1.0]hept-4-en-3-yl hydroperoxide, respectively. Hydroperoxy endoperoxide was reduced with aqueous sodium bisulfite; hydroperoxy-epoxide with dimethylsulfide-titanium tetraisopropoxide to give 7-oxabicyclo[4.1.0]hept-4-en-3-ol. Acidic hydrolysis of the epoxy-alcohol gave the (1,4/2)-cyclohex-3-ene-triol. Oxidation of the double bond with KMnO4 resulted in the formation of (+/-)-proto-quercitol.

A Novel Synthesis of DL-proto-, and DL-vibo-Quercitol via 1, 4-Cyclohexadiene

Abstract Photooxygenation of 1, 4-cyclohexadiene 3 followed by reduction with LiAlH4 or thiourea gave (25/1)-cyclohex-3-ene-triol 7a. trans-Hydroxylation of triol 7a with three different methods afforded both of proto-quercitol la and vibo-quercitol 2a.

Beneficial interaction of nimesulide with NSAIDs

In this study, the effects of nimesulide on the antiinflammatory and ulcerative action of some nonsteroidal antiinflammatory drugs (NSAIDs; (diclofenac sodium, ibuprofen, meloxicam) were investigated in rats, and it was determined whether nimesulide interacts with these drugs in vivo and in vitro. Results showed that while diclofenac sodium, ibuprofen, and meloxicam reduced carrageenan-induced paw edema in rats by 66%, 39.6%, and 58%, respectively, when used alone, they reduced carrageenan-induced paw edema by 69.8%, 56.6%, and 66%, respectively, when combined with nimesulide. Diclofenac (25 mg kg-1) and meloxicam (7.5 mg kg-1) produced 9.3 and 19.6 mm2 ulcer areas in stomachs of rats, respectively, when used alone, but when combined with nimesulide diclofenac and meloxicam did not cause any injury in rat stomachs. While ranitidine at 100 mg kg-1 dose prevented diclofenac-induced ulcer formation, it reduced meloxicam-induced ulcer formation significantly. We conclude that nimesulide does not interact with these drugs in terms of antiinflammatory action and antagonizes their side effects on gastric tissue without reacting chemically.