Abstract
Chemotherapy is one of the main treatment options for cancer, but it is usually accompanied with negative side effects. The classical drugs combination with synergistic adjuvants can be the ...solution to this problem, allowing reducing therapeutic dose. Elucidating the mechanism of adjuvant action is of key importance for the selection of the optimal agent. Here we examine the system drug-adjuvant to explain the observed effect in practice. We used the first line drug cisplatin. Morpholinium and 4-methylpiperazinium 4,5-dichloro isothiazol-3-carboxylates were selected as adjuvants. The study of the cisplatin-adjuvant system was carried out by quantum chemical modeling using DFT. It turned out that adjuvants form conjugates with cisplatin that lead to the relocation of frontier molecular orbitals as well as increase of conjugate’s dipole moment. It resulted in change of the interaction character with DNA and increase of the bioactivity of the system. The data obtained are the basis for expanding the studies to include other drugs and adjuvants. Oncologists will have opportunity to use “classical” chemotherapy drugs in combination with synergists for those patients who have not been previously recommended to such a treatment because of pronounced toxic side effects.
An unravelling of master equation for a set of fields interfering with one another is developed and conditions are found under which decoherence can be avoided for conditional and unconditional ...evolution of one of these fields.
In-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is 5-6%. Consequently, it is necessary to develop fundamentally novel drugs capable of reducing mortality in ...patients with acute myocardial infarction. Apelins could be the prototype for such drugs. Chronic administration of apelins mitigates adverse myocardial remodeling in animals with myocardial infarction or pressure overload. The cardioprotective effect of apelins is accompanied by blockage of the MPT pore, GSK-3β, and the activation of PI3-kinase, Akt, ERK1/2, NO-synthase, superoxide dismutase, glutathione peroxidase, matrix metalloproteinase, the epidermal growth factor receptor, Src kinase, the mitoK
channel, guanylyl cyclase, phospholipase C, protein kinase C, the Na
/H
exchanger, and the Na
/Ca
exchanger. The cardioprotective effect of apelins is associated with the inhibition of apoptosis and ferroptosis. Apelins stimulate the autophagy of cardiomyocytes. Synthetic apelin analogues are prospective compounds for the development of novel cardioprotective drugs.
An analysis of published data and the results of our own studies reveal that the activation of a peripheral δ
-opioid receptor (δ
-OR) increases the cardiac tolerance to reperfusion. It has been ...found that this δ
-OR is localized in cardiomyocytes. Endogenous opioids are not involved in the regulation of cardiac resistance to reperfusion. The infarct-limiting effect of the δ
-OR agonist deltorphin II depends on the activation of several protein kinases, including PKCδ, ERK1/2, PI3K, and PKG. Hypothetical end-effectors of the cardioprotective effect of deltorphin II are the sarcolemmal K
channels and the MPT pore.
Over the last three decades, treatment of stroke and acute myocardial infarction (AMI) has been improved, but it has stagnated in the last few years. Patients with stroke and AMI are admitted with ...formed ischemic injury of the brain or the heart, thereby it is difficult to affect this injury. However, it was possible to affect reperfusion injury of the brain or the heart. Ischemic damage to the lung is observed in pulmonary embolism. Ischemia and reperfusion of kidneys are observed in kidney transplantation. Significant progress in an increase in the efficacy of kidney transplantation, in treatment of stroke, pulmonary embolism, and AMI can be achieved through the development of novel drugs capable of preventing reperfusion injury of the brain or the heart with high efficiency. Synthetic apelin analogues with a long half-life could be prototypes of such drugs. It was found that apelins can increase tolerance of the heart, the brain, the lung, and the intestine to ischemia/reperfusion (I/R). Protein kinases are involved in the neuroprotective, cardioprotective, renoprotective, and pulmonoprotective effects of apelins. Mitochondrial permeability transition pore and ATP-sensitive K
+
channels are also involved in the protective effects of apelins. Apelins inhibit apoptosis and ferroptosis. Apelins activate autophagy of cardiomyocytes. Enzyme-resistant apelin analogues are perspective peptides for treatment of AMI, stroke, and I/R injury of lungs and kidneys.
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