Rational Drug Design for New Kinase Inhibitors


 Drug Designing: Open Access (ISSN 2169-0138) presents up-to-date coverage of advanced drug systems and their applications in medicine. Moreover, it brings the latest advances in fast-moving areas such as new drug approvals, covering all aspects of theory, research and application of diverse disciplines about Medicinal Chemistry Research and drug discovery and design.

In the most basic sense, drug design involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it. Drug design frequently but not necessarily relies on computer modeling techniques.Rational drug design refers to the development of medications based on the study of the structures and functions of target molecules. The role of rational drug design, besides developing effective drugs, is to avoid having to wait for pure luck to design a new drug or to use a shotgun approach in drug design.

The development of new drugs can present several problems, it is a important obstacle the ability to adapt a molecule that is a potent pharmacological inhibitor and that is also possible to execute its synthesis. Quinazolines are known to be capable of inhibiting kinases. Thus, a detailed study was carried out to propose new quinazolines with already known synthetic routes, and that were promising for the ability to inhibit kinases. A drug candidate molecule shall be proposed to have a good absorption, an extensive distribution so it’s capable of reaching the desired therapeutic targets. Lipinski's Rule of 5 in computational studies has been applied to select more promising molecules. In this study, the molecules proposed for the synthesis were systematically designed in appropriate computational programs to test several substituents of the quinazoline nucleus on the capacity of these molecules to be considered inhibitors of kinases. Six molecules were selected with the best results to inhibit kinases. In the study to evaluate the variation of substituents, the result obtained for the 8-position of the quinazoline ring and with the -Cl substituent at that ring position presented 60% of the 10 best molecules capable of inhibiting kinases. The molecular docking study confirmed that the two most promising molecules to inhibit kinase also obtained the best results to inhibit AKT kinase. Therefore, through this study it was possible to select six more promising molecules to be synthesized and available in large screening tests for several therapeutic targets known as High-Throughput Screening.

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Sherry Peterson
Journal Manager
Journal Drug Designing: Open Access
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