Abstract
Introduction: Charcot Marie Tooth Disease-2 is a debilitating neurogenetic disorder that adversely affects peripheral neurons by disrupting mitochondrial activity. Mutated mitofusin-2 (MFN) is the main culprit behind disruptive mitochondrial function and is considered a therapeutic target in identifying drugs for treating this disease. This disease has no therapeutic medication except for supportive care.
Objective: The objective of the current study is to evaluate high-affinity medicinal compounds for mutated MFN-2 and describe their absorption, distribution, metabolism, excretion, and toxic attributes (ADMET).
Methods: For ADMET properties, 2,219 medicinal compounds were analyzed with AutoDock Vina using PyRX 0.9 software against MFN-2, SwissADME, and GUSAR.
Results: Results from screening studies revealed that three compounds (Liriodenine, Pinocembrin, and Vestitol) show an affinity for amino acids present in the predicted active interface of the MFN-2 protein. Moreover, these compounds render low toxicity and efficient ADME qualities, combined with bloodbrain barrier permeability, drug-likeness, and lead-likeness.
Conclusion: Liriodenine, pinocembrin and vestitol are therapeutic compounds for CMT-2 treatment and should be used in further in vitro studies to confirm the results of this research.
