Cell Culture Characterization of Prooxidative Chain-Transfer Agents as Novel Cytostatic Drugs

Prooxidative therapy is a well-established concept in infectiology and parasitology, in which prooxidative drugs like artemisinin and metronidazole play a pivotal clinical role. Theoretical considerations and earlier studies have indicated that prooxidative therapy might also represent a promising strategy in oncology. Here, we have investigated a novel class of prooxidative drugs, namely chain-transfer agents, as cytostatic agents in a series of human tumor cell lines in vitro. We have found that different chain-transfer agents of the lipophilic thiol class (like dodecane-1-thiol) elicited half-maximal effective concentrations in the low micromolar range in SY5Y cells (human neuroblastoma), Hela cells (human cervical carcinoma), HEK293 cells (immortalized human kidney), MCF7 cells (human breast carcinoma), and C2C12 cells (mouse myoblast). In contrast, HepG2 cells (human hepatocellular carcinoma) were resistant to toxicity, presumably through their high detoxification capacity for thiol groups. Cytotoxicity was undiminished by hypoxic culture conditions, but substantially lowered after cellular differentiation. Compared to four disparate, clinically used reference compounds in vitro (doxorubicin, actinomycin D, 5-fluorouracil, and hydroxyurea), chain-transfer agents emerged as comparably potent on a molar basis and on a maximum-effect basis. Our results indicate that chain-transfer agents possess a promising baseline profile as cytostatic drugs and should be explored further for anti-tumor chemotherapy.

Synthesis of Chain Transfer Agents for RAFT Polymerization by using DBU

Trithiocarbonate TTC, Dithioester DT containing RAFT chain transfer acid agents are efficiently and conveniently esterified by DBU. The significance of the reaction is mild reaction condition, high yield, easy simple workup, and reduction of reaction time. This protocol providing a useful alternative method for ester synthesis and makes the process very viable or more economic.

FIRE SAFETY OF HEAT-TRANSFER AGENTS FOR HEAT GENERATORS

Рассмотрены свойства двух групп теплоносителей, используемых для понижения рабочей температуры и для повышения рабочей температуры. В первую группу теплоносителей включены: этиленгликоль, диэтиленгликоль, триэтиленгликоль, пропиленгликоль, глицерин. Вторую группу теплоносителей составляют: дифенильная смесь, масло АМТ-300, масло ТЛВ-330, мобильтерм-600, дикумилметан, дитолилметан, тетрахлордифенил, тетракрезилсиликат, нафталин, тройная нафталиновая смесь, нитрит-нитратная смесь. Приводятся физико-химические и пожароопасные свойства названных теплоносителей, а также перечень профилактических противопожарных мероприятий и средств пожаротушения. There are considered the properties of two groups of heat-transfer agents used to reduce the operating temperature and to increase the operating temperature. The following substances are included in the first group of heat-transfer agents: ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, glycerin. The following substances are included in the second group of heat-transfer agents: diphenyl mixture, AMT-300 oil, TLV-330 oil, mobileterm-600, dicumylmethane, ditolylmethane, tetrachlorodiphenyl, tetracresyl silicate, naphthalene, triple naphthalene mixture, nitrite-nitrate mixture. There are cited the physicochemical and fire hazardous properties of the mentioned heat-transfer agents, as well as the list of preventive fire-fighting measures and fire-extinguishing facilities.

Immunopharmacological Properties of Methacrylic Acid Polymers as Potential Polymeric Carrier Constituents of Anticancer Drugs

Cytostatic chemotherapeutics provide a classical means to treat cancer, but conventional treatments have not increased in efficacy in the past years, warranting a search for new approaches to therapy. The aim of the study was, therefore, to obtain methacrylic acid (MAA) (co)polymers and to study their immunopharmacological properties. 4-Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl] pentanoic acid (CDSPA) and 2-cyano-2-propyl dodecyl trithiocarbonate (CPDT) were used as reversible chain transfer agents. Experiments were carried out in Wistar rats. The MTT assay was used to evaluate the cytotoxic effect of the polymeric systems on peritoneal macrophages. An experimental tumor model was obtained by grafting RMK-1 breast cancer cells. Serum cytokine levels of tumor-bearing rats were analyzed. The chain transfer agents employed in classical radical polymerization substantially reduced the molecular weight of the resulting polymers, but a narrow molecular weight distribution was achieved only with CDSPA and high CPDT concentrations. Toxicity was not observed when incubating peritoneal macrophages with polymeric systems. In tumor-bearing rats, the IL-10 concentration was 1.7 times higher and the IL-17 concentration was less than half that of intact rats. Polymeric systems decreased the IL-10 concentration and normalized the IL-17 concentration in tumor-bearing rats. The maximum effect was observed for a MAA homopolymer with a high molecular weight. The anion-active polymers proposed as carrier constituents are promising for further studies and designs of carrier constituents of drug derivatives.