Abstract
Neurodegenerative disorders follow numerous pathological ways concerning overexpression of monoamine oxidase and formation of reactive oxygen species. The computational design of the piperine derivatives has given the significant MAO inhibitors with considerable antioxidant potential. Molecular docking provided the mechanistic insight of the compounds within the hMAO active site. In the current study we have prepared a series of compounds related to piperine and investigated them through monoamine oxidase A and B assay and evaluated the free radical scavenging activity. The synthesized compounds were analyzed by using in silico techniques within the active site of MAO and the ADMET properties were also calculated. The results obtained in this study indicated the interesting therapeutic potential of some compounds such as 7and 17c as most promising hMAO-A inhibitors whereas compounds 15, 5 and 17b were found as hMAO-B inhibitors. Moreover, we assessed the antioxidant potential of the piperine analogues and compounds 5, 17b, and 7 showed very modest antioxidant activity against DPPH and H2O2 radicals. The outcome of the study indicating that the piperine related derivatives are found as considerable MAO inhibitors and antioxidants. Moreover, the SAR structure activity relationships are depicting the structural features required for the MAO inhibition. In case of MAO activity, good correlations were found among the calculated and experimental results.
Highlights
The elementary nature of both monoamine oxidases (MAO, EC 1.4.3.4) isoforms (MAO-A and MAO-B) in the catabolism of monoaminergic neurotransmitters has been widely studied [1]
Synthesis of the acyl chloride was definite subsequent wave number point in IR spectra peaks: carbonyl group confirm up approximately: 1684 cm−1 with the plain bond of OH group was noticed about 3448 cm−1 in the preparatory acid while the carbonyl of the acyl chloride shifted the peak around 1749 cm−1
The progress of the reaction was cheeked through thin layer chromatography Thin layer chromatography (TLC) executed on 0.25 mm pre-coated plates with silica gel procured from Merck, and the spots were envisaged in iodine chamber and UV cabinet, in mobile media TLC-hexane:toluene:ethyl acetate (1:1:1)
Summary
The elementary nature of both monoamine oxidases (MAO, EC 1.4.3.4) isoforms (MAO-A and MAO-B) in the catabolism of monoaminergic neurotransmitters has been widely studied [1]. The crystallographic MAO structure comprised of three functional domains in the active core, called the entrance cavity, substrate cavity, and the “aromatic cage” [5] This “aromatic cage” is created by Tyr435 and Tyr398 for MAO-A) whereas Tyr407 and Tyr444 for MAO-B with FAD (redox cofactor), and with some heterocyclic or aromatic compounds co-crystallized within an active site [6]. This information enthusiastically revived the interest of medicinal chemists to explore the rational design of selective and effective MAO inhibitors without undesirable side effects. Among all explored natural products piperine has been extensively studied for the MAO inhibition and has shown the significant potential to be an applicable candidate for neurological disorders [8]
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