Some non-differentiation-induction benzo[a]phenothiazines and mutagenic benz[c]acridines more potently inhibited the mitogen-induced blast transformation of human-peripheral blood lymphocytes than differentiation-induction and non-mutagenic counterparts and phenothiazines. Differential absorption spectrophotometry revealed tight complex formation between these drugs and bacterial endotoxin or mitogens. All of these compounds only slightly affected antibody dependent cellular cytotoxicity and natural killer cell activity, but significantly inhibited the endotoxin-or heat-killed Staphylococcus aureus induced tumor necrosis factor production by human mononuclear cells. Pretreatment of mice with these drugs protected them from lethal E. coli infection. Quantumchemical analysis suggests a correlation between the biological activity of these compounds and some molecular orbital parameters such as the charge at C7, and the ratio of polar/total surface areas.
The structure-activity relationship of the cytotoxic activity of azulene and azulene derivatives was discussed, using theoretically calculated results. In order to clearly divide the azulenes into three groups according to their functional groups, the CC50, four different dipole moments (muG, muESP-G, muwand muESP-W) and heats of formation (deltaHf) of the azulenes [1-24] were separately calculated in two states, gas-phase and water, by the conductor-like screening model/parametric method 3 (COSMO/PM3). For the halogenated azulenes and isopropyl azulenes, the cytotoxic activity might follow the three quantitative structure-activity relationship (QSAR) parameters: deltadeltaHf, HOMO energy and muw Whereas, for the other ten compounds [3-5, 7-8, 10, 15-18], the cytotoxic activity might be related to the three QSAR parameters, deltadeltaHf, LUMO energy and muG
Electronic interaction of DNA with nine benzacridine derivatives was studied. The interaction system of these benzacridines and DNA was found to show a marked hypochromism in the ultraviolet region. The orderly double helical structure of DNA was found to play an essential role in this spectroscopic change. A high concentration of the interactant, low environmental ionic strength, low pH, and low temperature were beneficial in this interaction. The degree of hypochromism expressed by the integrated and pKa of the benzacridines were found to be in parallel. The hypochromism of the interaction system, in which the carcinogenic benz[c]acridine derivatives took part, was larger than that of the system in which the noncarcinogenic derivatives were involved.
Coenzyme Q 10 (CoQ 10 ), a lipid soluble quinone, is a constituent of the mitochondrial respiratory chain and plays a key role in the synthesis of adenosine triphosphate (ATP) by oxidative phosphorylation. It is also a potent antioxidant, acting at both the cellular and subcellular level. On the basis of its antioxidant properties and its role in energy production, CoQ 10 has been used to treat a wide variety of cardiovascular disorders. There is evidence for beneficial effects of CoQ 10 in the treatment of heart failure, hypertension and ischaemic heart disease. CoQ 10 pre-treatment has also been shown to have beneficial effects in patients undergoing cardiac surgery. The mechanism of these effects is multifaceted with increased energy production, protection against lipid peroxidation and attenuation of ischaemia reperfusion injury all contributing to the improvements demonstrated after CoQ 10 therapy. In this chapter, we outline the rationale and evidence for the use of CoQ 10 in these conditions.
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