RESUMO
Alzheimer's disease is a widespread type of neurodegenerative dementia that mainly affects the elderly. Currently, this disease can only be treated palliatively. Existing drugs can only improve patients' symptoms. The search for new drugs that can effectively treat this disease is an important field of research in medicinal chemistry. Here we report a structure-activity relationship study of tacrine and some of its analogues in relation to their inhibitory activities against Alzheimer's disease. All of the molecular descriptors were calculated at the M062X/6-311++G(d,p) level of theory. Principal component analysis of the molecular descriptors showed that the compounds could be categorized into active and inactive compounds using just two descriptors: the HOMO and LUMO energies. These results should help us to explain the activities of tacrine derivatives and to model new tacrine analogues that are active against Alzheimer's disease. Graphical abstract PCA score plot for tacrine and its analogues.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/química , Relação Estrutura-Atividade , Tacrina/química , Doença de Alzheimer/patologia , Inibidores da Colinesterase/uso terapêutico , Humanos , Modelos Moleculares , Análise de Componente Principal , Tacrina/análogos & derivados , Tacrina/uso terapêuticoRESUMO
Nitric oxide (NO) is an important chemical compound involved in many physiological and pathological processes in living organisms. However, nitric oxide is a very reactive radical that needs to be carried through organisms to reach the desired biological target. With the aim of developing new compounds that can be used as biomedical NO carrier agents we carried out a theoretical investigation at B3LYP/6-31+G(d)/LANL2DZ level on the interaction of NO with RuTAP (Ruthenium tetraazaporphyrin) and Ru(L)TAP, where L=Cl-, NH3, and Pyridine (Py)) and the oxidation state of Ru ranging from +1 to +3. The theoretical calculation results show that the geometric and electronic parameters of the Ru-NO bond are highly dependent on the oxidation state of Ru and of the chemical nature of ligand L at axial position. The results also show clearly that RuTAP and Ru(L)TAP are good potential candidates to be used as NO carriers in living organisms.
