K. A. Abzaeva

Metal polyacrylates, ferrocene derivatives, and polysuccinimide as potential antitumor drugs

Compounds belonging to three novel groups of oncological drugs (metal polyacrylates, ferrocene derivatives, and polysuccinimide) showed antitumor activity. The most efficient compounds, viz., gold polyacrylate (auracryl), 2-[(1-ferrocenylethyl)sulfanyl]pyrimidine (LS-17), and polysuccinimide, inhibit the growth of murine solid tumors by 70–95% and are recommended for further thorough preclinical studies of their antitumor properties and mechanisms of action.

Modern topical hemostatic agents and unique representatives of their new generation

Representatives of modern topical hemostatics used most widely in practical medicine, which are conventionally divided according to their nature and mechanism of action, are analyzed. The results of innovative design of new-generation styptics based on polymetalloacrylates are summarized. Potential hemostatic agents with unique properties that can serve as versatile means for rapid blood clotting in a variety of surgical procedures, even for patients with impaired blood coagulation and upon wounds and injuries in emergency situations, for considerable acceleration of wound healing, repair regeneration process in skin burns due to their antimicrobial and anesthetic properties are proposed.

Polyacrylates of noble metals as potential antitumor drugs

The antitumor activity of polyacrylates of the noble metals containing argentum (argacryl), aurum (auracryl) and platinum (platacryl) has been studied using experimental murine solid tumor models (Lewis lung carcinoma and Acatol adenocarcinoma). It has been found that polyacrylates of the noble metals are capable of inhibiting tumor development by 50–90% compared to control. Auracryl that inhibits the growth of Lewis lung carcinoma and Acatol adenocarcinoma by 80 and 90%, respectively, compared to control is the most efficient among the tested compounds and can be recommended for the further profound preclinical studies.

Phenyltrifluorosilane in organoelemental and organic synthesis

Ways of phenyltrifluorosilane application in organoelementalal and organic synthesis are summarized and systematized for the first time. The methods of its synthesis, physicochemical properties, and reactivity are considered. Special attention is paid to the original experimental results obtained by the authors.

Cellular effects of the antitumor drug aurumacryl

The cellular effects of aurumacryl (a drug based on gold polyacrylate, which previously showed significant antitumor activity in vivo against solid tumors in mice) were studied in the model of the MCF7 stable cell line of human breast carcinoma. It was found that aurumacryl possesses cytotoxic and cytostatic effects on tumor cells. The dose-dependent cytotoxic effect of aurumacryl is expressed as the death of 60% of tumor cells after incubation with aurumacryl at a dose of 1 mg/mL for 24 h. The proliferation kinetics of the surviving fraction of tumor cells also undergoes significant changes, which is expressed in the predominant accumulation of the cells (93%) in the G0 phase of proliferative rest and in a significant decrease in the number of proliferating cells to 7%. These data could be interpreted as evidence of the loss of the reproductive ability of the surviving cells after treatment with aurumacryl.

PHARMACOLOGICAL ACTIVITY OF ZIACRYL, A ZINC SALT OF POLYACRYLIC ACID

The pharmacological properties of the new drug ziacryl (feracryl analog), representing an incomplete zinc salt of polyacrylic acid, have been studied. It is established that ziacryl is a highly effective hemostatic agent that exhibits antimicrobial activity and accelerates the regeneration of skin burn lesions and asceptic wounds.

Solvatochromism of heteroaromatic compounds : XII. solvatochromism and tautomerism of 4-methyl-3-nitro-1,2,4-triazol-5-one in aprotic solvents

The long-wave absorption band in the UV spectrum of 4-methyl-3-nitro-1,2,4-triazol-5-one is highly sensitive to specific solvation by hydrogen bonding with a protophilic solvent. The UV and IR spectra suggest that the compound mainly exists in the form of the N1H tautomer. The qualitative and quantitative relationships characterizing the solvent effect on the spectral characteristics of the major tautomer were elucidated.

Antimicrobial and Hemostatic Effects of Silver Salts of Poly(acrylic Acid)

As is known, metal (Cu, Zn, Co, Ni, and Fe) polyacrylates possess weak antimicrobial activity determined to a considerable extent by the content of the metal in the polymer macromolecule [1]. For example, the well-known hemostatic feracryl, representing the incomplete iron salt of poly(acrylic acid) (PAA) with an iron content varying from 0.05 to 0.5% [2, 3], exhibits antimicrobial activity with respect to Ps. aeruginosa and St. aureus, which increases when the iron concentration in the system grows. However, a high Fe concentration in PAA leads to undesired crosslinking of the polymer macrochains and to the loss of solubility of iron polyacrylate. Medicine has employed the antiseptic properties of silver solutions and salts for more than a century in fighting harmful bacteria and viral infections [4, 5]. The purpose of our study was to obtain incomplete silver salts of PAA for creating a preparation combining antimicrobial and hemostatic properties. For this purpose, we synthesized a series of silver-containing PAA derivatives (I – VIII) with the macromolecules containing 1 to 10% Ag (Table 1). The products correspond to the general formula

Antimicrobial and Hemostatic Effects of Silver-Containing Poly(acrylic acid) Derivatives

Poly(acrylic acid) (PAA) effectively interacts with blood proteins to form intermolecular complexes, thus producing a hemostatic effect [1]. This effect was used to develop the well-known hemostatic feracryl representing an incomplete iron salt of PAA containing 0.05 – 0.5% Fe. This drug possesses weak antimicrobial properties, which tend to increase when the iron content grows to 2.5% [1 – 3]. A higher Fe concentration in PAA leads to undesired crosslinking of the polymer macrochains and the loss of solubility. In practice, medicine widely employs antiseptic silver-containing preparations (protargol, collargol, sulfargin, poviargol) [4, 5] exhibiting a broad spectrum of antimicrobial activity with respect to both Gram-positive and Gram-negative bacterial species, including those resistant to antibiotics. Aiming at the development of a drug combining high antimicrobial and hemostatic efficacy, we have synthesized a series of silver-containing PAA derivatives. The complex, containing 4 to 10% silver and conventionally called argacryl, has the general formula (–CH2–CHCOOH)n– (–CH2–CHCOOAg)m with n = 9000 – 40,000 and m = 100 – 3000 and a molecular weight of (1 – 3) 10. The IR spectra of argacryl (recorded as KBr pellets with a Specord IR-75 spectrophotometer) are identical to those of feracryl, containing absorption bands due to carboxy, carboxylate, and hydroxy groups at 1720, 1570, and 3400 cm – , respectively. The antibacterial and hemostatic effects of argacryl were studied in comparison to the analogous properties of the PAA matrix and feracryl. EXPERIMENTAL BIOLOGICAL PART

Complex of tris(2-hydroxyethyl)amine and zinc bis(2-methylphenoxyacetate) as inhibitor of acid cholesterol esterase synthesis in blood platelets and mononuclear cells

Application of tris(2-hydroxyethyl)amine and zinc bis(2-methylphenoxyacetate) complex (zincatrane) in experimental atherosclerosis in rabbits leads to decrease in the levels of cholesterol and total lipids in blood platelets (Tc) and monocytes (Mc). The results of enzymatic analysis show that atherogenesis is accompanied by increased activity of acid cholesterol esterase by 66% in Mc and by 55% in Tc compared to standard values. Intramuscular administration of zincatrane at a dose of 10 mg kg−1 decreases the activity of acid cholesterol esterase by almost 35% in Mc and by 26% in Tc compared to the control group. It has been also revealed that zincatrane possesses heparin-like effect, which is expressed in increased thrombin clotting time, blood clotting time and plasma recalcification time as well as in the decreased thrombocyte aggregation. It is assumed that zincatrane stimulates production of endogenous heparin.