Malaria is a communicable disease which is caused by protozoan's mainly Plasmodium species (P. falciparum, P. ovale, P. vivax, P. malariae and P. knowlesi). The increasing resistance of Plasmodium to available malarial drugs poses a great responsibility for the researchers in the field of malaria. To overcome this problem of resistance, this study aimed to design and synthesize a new class of antimalarial agent with chalcone as the main moiety. Chalcones, a member of flavanoid family, consist of two aromatic rings of 1,3-diphenyl-2-propen-1-one linked by a three carbon α,β-unsaturated carbonyl system. Five derivatives were designed and among them one was selected. The CC2 was then synthesized by esterification of Para amino acetophenone followed by treatment with hydrazide to form 2-(4 acetylphenoxy) acetohydrazide. This was then coupled with 2-Bromo substituted Diazotized esterified anilines, which was finally linked with substituted benzaldehyde to yield CC2. These were then structurally verified by Infra Red (IR) and Nuclear Magnetic Resonance (NMR) spectroscopy. The chalcone was then tested for in vitro growth inhibition assays using SYBR GREEN-1 Based assay and IC 50 values were identified. The compound CC2 showed quite promising antimalarial activity by inhibiting cysteine protease enzyme. The acute toxicity studies of the compound were carried out as per OECD guideline 425 and the results showed no toxic signs and symptoms indicating CC2 as a safe and less toxic compound.
Background The study aimed to design, synthesize and evaluate various brominated derivatives of 7-hydroxy coumarin as a new scaffold against Alzheimer’s disease by in vivo and in vitro models. A group of three novel pyrazoles endowed with brominated 7-hydroxy 4-methyl coumarin derivatives were designed. Among the designed compounds, a single entity (D1) was selected based on the docking score, which could be considered mainly for the treatment of Alzheimer’s disease. Three novel pyrazoles endowed with brominated 7-hydroxy 4-methyl coumarin derivatives were designed and docking studies of these compounds were carried out using Argus lab4.0.1 version. According to the docking score, a single entity of compound (D1) was selected for further study. The structure of the compound (D1) was explored by spectral analysis. The anti-Alzheimer’s activity was evaluated by in vivo and in vitro methods. All results were compared statistically by one-way ANOVA using GraphPad Prism. Results Molecular docking studies revealed that the compound D1 was able to bind simultaneously to the amino acid and in the active sites of the acetylcholine esterase enzyme. In acetylcholine esterase inhibition assay, the compound shows a significant increase in acetylcholine esterase level. The MAO inhibitory activities were in the nanomole range (human MAO-A IC50 = 3.9, human MAO-B IC 50 = 4.4). DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay showed that the compound shows a promising antioxidant property. In the evaluation of learning and memory of compound D1 using elevated plus maze, the compound D1-pretreated group showed a significant increase in memory and learning when compared with donepezil. Conclusions Among the designed series of pyrazole endowed with brominated 7-hydroxyl 4-methyl coumarin derivatives, compound D1 showed good antioxidant property and acetylcholine esterase and MAO inhibitory activity; based on this property, the synthesized compound D1 can be considered a new scaffold on Alzheimer’s disease.
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