Qsar Studies On Medicinal Activity Based On Quantum Chemical Calculations

Quantitative structure-activity relationship (QSAR) is a method of predicting molecular chemistry characteristics from the parameters of physical-chemical and molecular structure. QSAR researches the molecule simulation, which based on quantum chemical computation, were combined to offer a new route to seek several precursor compounds with biologic and medical activity. With quantitative structure-activity relationship analysis, it is possible to analyze the probable structural elements affecting the biological activity of compounds. The information can be used in designing new bioactive compounds and exploring the mechanism of drugs.In this thesis, the QSAR studies for antimycobacterial activity of aldose reductase inhibitors, chemokine receptor antagonist, 6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid derivatives, selective inhibitor of cyclooxygenase-2 were carried out by using partial least-squares regression, exhaustive linear regression and chaos genetic neural network. According to these models, we discussed the effects of these parameters on inhibitory activity.Diabetes is a chronic disease which is very harmful to people's health. It is the third factor leading human to death, inferior to cardiovascular diseases and tumor. Diabetes control and complications is the main reason for diabetes death and disability. The studies have shown that the increased activity of aldose reductase leading to diabetes control and complications, so inhibiting aldose reductase can be a strategy for diabetic complications. We herein describe analysis of 2, 4-thiazolidinediones as inhibitors of aldose reductase.The relevance of the QSAR model obtained for the design of novel derivatives should be assessed not only in terms of predictivity, but also in terms of their ability to provide a chemical and structural explanation of their binding interaction. The results obtained here will be useful for the design of new aldose reductase inhibitors.The human acquired immunodeficiency syndrome (AIDS) is mainly due to human immunodeficiency virus type 1 (HIV-1) infection, which is rapid propagation of the body and lead to damage huge amount of white blood cells. Despite worldwide efforts to prevent the spread of HIV-1, the number of HIV-1 infected people still continues to rise. CCR5, a membrane protein on cell surface, is a member of G protein-coupled receptor superfamily and one of the major co-receptors for HIV-1 infection was received with excitement in the scientific community as a potential new target for antiviral therapy. In this paper, the quantitative structure-activity relationship studies on CCR5 antagonist, according to the results of QSAR studies, we put forward a number of high activities of CCR5 antagonist in theory, and look forward to experimental confirmation. The QSAR results can offer a theoretical reference for the pharmaceutical synthesis.Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (MTb).The World Health Organization estimates that one third of the world's population is infected by Mycobacterium tuberculosis. Each year, there are about 8 million new TB cases and 2 million deaths worldwide. TB was declared a global health emergency by the WHO in 1993 and 2004 respectively. In this paper, the quantitative structure-activity relationship studies on 6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid derivatives, The QSAR results can provide theoretical reference for syntheticing such drugs with a higher antimicrobial activity.Non steroidal anti-inflammatory drugs are the first line therapy for the treatment of arthritis and block the metabolism of arachidonic acid through inhibition of cyclooxygenase and thereby production of prostaglandins (PGs). Cyclooxygenase-2 is not expressed in most of normal tissues, but it is synthesized rapidly to take part in inflammation course and oncogenesis when cells are stimulated by various kinds of stimuli, such as cytokines, inflammatory agent and induced by carcinogenic agent. Further and thorough research on cyclooxygenase-2 will provide a new target for new non-steroidal anti-inflammatory drugs. In this paper, we build the quantitative relationship between drug activities with the structure of 1, 2-diaryl imidazole as cyclooxygenase-2 selective inhibitor, the calculated parameters effect on antibacterial activity was discussed in detail based on the QSAR results, providing theoretical guidance for finding highly active non steroidal anti-inflammatory drugs.