Primary screening of new non-steroid anti-inflammatory drugs in the lin of original biometallic dihydroxo-µ-bis(gluconato)digermanates(IV)

Abstract

Nowadays, there are no anti-inflammatory drugs, that would optimally fit clinical conditions. That's why
there is an active search for new anti-inflammatory drugs, which would exceed the existing analogues in
effectivity and/or safety. In this regard, there is a perspective in germanium containing coordination compounds, to which wide spectrum of pharmacological activity, including anti-inflammatory is inherent. In preliminary studies we have shown low toxicity (LD50 > 2000 mg/kg) and pronounced antihypoxic activity in biometallic dihydroxo-µ-bis(gluconato)digermanates(IV). The aim of the study – to carry out primary screening of anti-inflammatory activity among original biometallic dihydroxo-µ bis(gluconato)digermanates(IV) and to determine the most promising compounds compared with referent drug. Antiexudative activity of biоmetallic dihydroxo-µ-bis(gluconato)digermanates, which contain ions of
nickel, manganese, magnesium, cobalt, copper or zinc, have been studied on the model of exudative inflammation «carrageenan edema» in comparison with sodium diclofenac in white non-linear mice. Studied compounds were injected intraperitoneal once, 15 minutes before administration of flogogenic agent into aponeurosis of hind paw. Quantitative assessment of edema was carried out based on the paw
weight. As a result of the experiment it was established that by the level of anti-inflammatory effect studied
compounds can be arranged in the next sequence: nickel ≤ manganese ≤ magnesium ≤ cobalt ≤ copper ≤
diclofenac ≤ zinc. Shown, that introduction in the base structure of nickel, manganese or magnesium ions didn’t provide the reliable antiexudative effect, while presence of such ions as cobalt, copper or zinc caused pronounced anti-inflammatory effect: edema inhibition was 20,79%, 29,0% та 36,35% correspondingly. Compounds in used doses, that contain copper or zinc, show anti-inflammatory activity, comparable to that of reference drug sodium diclofenac. Accounting for the fact, that at this period of study the model of carrageenan edema characterizes cyclooxygenase path of inflammation, one can assume, the presence of anticyclooxygenase component of anti-inflammatory action of studied coordination compounds of
germanium.
Thus, the results obtained indicate the perspective of further studies of the most active biometallic
dihydroxo-µ-bis(gluconato)digermanates(IV) as promising NSAIDs.