CLINICAL RELEVANCE OF EFAVIRENZ PHARMACOKINETICS AND PHARMACOGENETICS IN HIV/AIDS THERAPY

Individuals respond to the same medications in diverse manners. Polymorphism in drug-metabolizing enzymes plays a very important role in interindividual variations in drug medical care. Hence, the aim was to review reported cases of genetic polymorphisms among the antiretrovirals, especially efavirenz, a non-nucleoside reverse transcriptase inhibitor, used in the management of human immunodeficiency virus infection/acquired immune deficiency syndrome, which is metabolized primarily by the CYP2B6 enzyme. Several previous publications on genetic polymorphism associated with the antiretrovirals of patients on highly active antiretroviral therapy were selected and carefully reviewed to evaluate their correlation and or conflict of interest among different authors. The existence of polymorphisms on the CYP2B6 gene that encodes for expression of the enzyme, among other factors responsible for efavirenz metabolism, is a significant determinant of inter-individual variability in pharmacokinetics and pharmacodynamic response to the drug used in clinical practice. Furthermore, plasma levels of efavirenz and phenotypic difference were observed, are contributing factors as to the rate of antiretroviral adverse drug reactions. Following the review, studies showed similar outcomes relating to efavirenz pharmacokinetics and polymorphism; hence, patients that display genetic polymorphism on efavirenz may likely develop the same on other therapeutic agents metabolized by the CYP450 enzymes or other polymorphic enzymes

CHARACTERIZATION AND MOLECULAR DOCKING OF CINNAMIC ACID DERIVATIVES: POTENTIAL INHIBITORS OF CYCLOOXYGENASE ENZYMES

Objective: The pathology of every disease passes through the inflammation stage; hence, the design and optimization of potential lead compounds as anti-inflammatory agents is still a significant part of medicinal chemistry globally. Methods: In this study, we designed, synthesized, and characterized some cinnamic acid derivatives and performed molecular docking of the derivatives on the human cyclooxygenase-1 (COX-1) enzyme. Results: The elemental analysis showed the presence of different functional groups. Molecular docking was performed on the active sites of COX-1 (PDB ID: 6Y3C). The derivatives as well as the standard compound, were observed to interact mainly with the arginine residue of the target protein. The dioxomethylene substituted derivative showed the highest binding affinity, compared with other derivatives, including the standard drug (−6.8 kcal/mol). Conclusion: The binding affinity observed in the cinnamic derivatives, and biological activities correlations revealed that compounds with the dioxomethylene group would be good anti-inflammatory lead molecules, as they demonstrated high affinity to the target protein and biological activities. Thus, these compounds can serve as potential lead compounds for the design, and development of effective anti-inflammatory agents, targeted to inhibit the human COX-1 enzyme involved in biological inflammatory mechanisms