Complex compounds of 8-hydroxyquinoline and their therapeutic activity
Abstract Generated abstract
This paper investigates complex compounds of 8-hydroxyquinoline with mercury salts as potential topical agents for psoriasis treatment, motivated by the therapeutic activity but high toxicity and irritancy of existing mercury preparations. The authors synthesized two 1:1 complexes, with potassium mercurorhodanide and potassium mercuroiodide, characterized them by mercury analysis and photocolorimetry, and report pharmacological testing showing toxicity 10 to 20 times lower than that of the organic component. Clinical use as 2 to 5 percent ointments in patients with psoriasis produced positive effects in all reported cases, without noticeable side effects or staining of skin and linen. The study suggests that complex formation may reduce toxicity while preserving therapeutic activity, and proposes further investigation of how complex structure and physicochemical properties affect physiological action.
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COMPLEX COMPOUNDS OF 8-HYDROXYQUINOLINE AND THEIR THERAPEUTIC ACTIVITY
A. T. Pechenkin, S. D. Yaroslavleva
(Presented by Prof. L. P. Kulev, Doctor of Chemical Sciences)
Psoriasis (scaly lichen) is one of the most widespread skin diseases. The etiology of psoriasis has not been sufficiently clarified, although it may be regarded as an undoubtedly established fact that some cases have a hereditary-parasitic character [1].
A variety of agents are used for the treatment of psoriasis [2]; however, what they most generally have in common is an antiseptic bactericidal action.
The most effective, but also the most irritating, agents used in psoriasis are salts of divalent mercury and psoriasin (an ointment containing 1/20000 part of yperite), but mercury salts and psoriasin cannot be used on the face or the hairy part of the head, since they may cause eye disease. They are also inapplicable on large areas of skin affected by psoriasis, since, upon absorption, they produce undesirable side effects, up to the picture of general poisoning.
Taking into account the vigorous action of mercury salts in psoriasis, it was of interest to us to obtain a series of complex compounds consisting of mercury salts and known organic antiseptics, and to test their effectiveness in the treatment of psoriasis. In doing so, we expected that the toxicity of such preparations would be much lower than the toxicity of mercury salts, which would make it possible to apply them to larger areas of skin affected by psoriasis than had been done up to now.
As was reported earlier [3], we obtained complex compounds of mercury salts with trypaflavine and rivanol. After pharmacological testing, the clinical trials that were conducted gave a positive result. However, a substantial disadvantage of these preparations for clinical practice is that they stain the patient’s skin and linen a bright yellow color.
Continuing the search for new medicinal preparations of a complex character, we obtained complex compounds of potassium mercurorhodanide with 8-hydroxyquinoline (preparation No. 82, m.p. = 130°) and potassium mercuroiodide with 8-hydroxyquinoline (preparation No. 83, m.p. = 142°). The indicated compounds were obtained in the form of greenish-yellow powders in quantitative yield by mixing concentrated aqueous solutions of the starting substances, taken in an equimolecular ratio. Both preparations are sparingly soluble in water, moderately soluble in alcohol. Quantit—
analysis for mercury and photocolorimetry (composition—percent light absorption, FEK—2 m, 50 mm cuvette, blue light filter) show that the complex compounds obtained have a composition of 1 : 1
\[ \begin{aligned} &\text{8-hydroxyquinoline}\cdot K_2Hg(CNS)_4 \qquad \text{8-hydroxyquinoline}\cdot K_2HgJ_4 \end{aligned} \]
Pharmacological tests of these preparations were carried out at the Department of Pharmacology of the Tomsk Medical Institute by Yu. M. Lonshakov. It was established that their toxicity is relatively low and is 10–20 times lower than the toxicity of the organic component of the complexes.
Clinical tests of the preparations obtained were conducted in the clinic of skin diseases of the Tomsk Medical Institute under the direction of Professor I. S. Beirakh. The preparations were used in the form of a 2–5% ointment on a petrolatum or lanolin base. Preparation No. 82 was used on 42 patients with psoriasis. The preparation was easily tolerated by the patients, without any undesirable side effects, both on small and on large areas of affected skin. In all 42 cases a positive clinical effect was obtained. Preparation No. 83 was used in 14 cases, likewise with a positive therapeutic effect. No noticeable difference in the action of these preparations was found. Both preparations do not stain the patient’s skin or linen.
Thus, the idea of reducing the toxicity of mercury compounds used in psoriasis therapy by means of the complex-formation reaction finds experimental confirmation and makes it possible to broaden the scope of research in this direction, in order to elucidate the influence of the chemical structure and physicochemical properties of complexes on their physiological activity in psoriasis.
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A. G. Pechenkin. Some complex compounds of the acridine series and their therapeutic activity, Izv. TPI, vol. 102, 1960.