In hatcheries, the adequate supply of live feed has a vital role in feeding fish larvae, fry and fingerlings. Furthermore, the enhancement of the nutritional quality of live feeds is well‐developed techniques in aquaculture. Essential fatty acids (EFA) such as docosahexaenoic acid (DHA; C22:6 n−3), eicosapentaenoic acid (EPA; 20:5(n−3) and arachidonic acid (ARA; 20:4(n−6) and amino acids are an essential source of proteins for larval rearing of fish. However, the common practised live feeds used for the primary feeding such as rotifers and Artemia are naturally deficient in essential nutrient components. Hence, the improvement of the nutritional quality of live feeds with different oil emulsions and commercial diets, and manipulation of the feed are necessary for fish production. The production protocols of copepods, Moina and fairy shrimps as live feed are still underdeveloped in hatcheries. The different lipid sources using for the enrichment of Artemia and rotifers are not effective on other live feeds, especially copepods and cladocerans (Moina, Daphnia) and fairy shrimps. This review focuses on the importance of live feeds by the techniques of feed enhancement or enrichment of zooplankton by direct incorporation of nutrients for feeding of early stages of fish.
The present AChE inhibitors have been successful in the treatment of Alzheimer׳s Diseases however suffers serious side effects. Therefore in this view, the present study was sought to identify compounds with appreciable pharmacological profile targeting AChE. Analogue of Rivastigmine and Fluoxetine hybrid synthesized by Toda et al, 2003 (dataset1), and Coumarin−Tacrine hybrids synthesized by Qi Sun et al (dataset2) formed the test compounds for the present pharmacological evaluation. p-cholorophenyl substituted Rivastigmine and Fluoxetine hybrid compound (26d) from dataset 1 and −OCH3 substitute Coumarin−Tacrine hybrids (1h) from dataset 2 demonstrated superior pharmacological profile. 26 d showed superior pharmacological profile comparison to the entire compounds in either dataset owing to its better electrostatic interactions and hydrogen bonding patterns. In order to identify still better compound with pharmacological profile than 26 d and 1h, virtual screening was performed. The best docked compound (PubCId: PubCid: 68874404) showed better affinity than its parent 26 d, however showed poor ADME profile and AMES toxicity. CHEMBL2391475 (PubCid: 71699632) similar to 1h had reduced affinity in comparison to its parent compound 1h. From, our extensive analysis involving binding affinity analysis, ADMET properties predictions and pharmacophoric mappings, we report p-cholorophenyl substituted rivastigmine and fluoxetine hybrid (26d) to be a potential candidate for AcHE inhibition which in addition can overcome narrow therapeutic window of present AChE inhibitors in clinical treatment of Alzheimer׳s disease.AbbreviationsAD - Alzheimer׳s Disease, AChE - Acetyl Choline Estarase, OPLS - Optimized Potentials for Liquid Simulations, PDB - Protein Data Bank.
Alteration of the acetylation status of chromatin and other non-histone proteins by HDAC inhibitors has evolved as an excellent epigenetic strategy in treatment of cancers. The present study was sought to identify compounds with positive pharmacological profiles targeting HDAC1. Analogues of Vorinostat synthesized by Cai et al, 2015 formed the test compounds for the present pharmacological evaluation. Hydroxamte analogue 6H showed superior pharmacological profile in comparison to all the compounds in the analogue dataset owing to its better electrostatic interactions and hydrogen bonding patterns. In order to identify compounds with even better high affinity and pharmacological profile than 6H and Vorinostat, virtual screening was performed. A total of 83 compounds similar to Vorinostat and 154 compounds akin to analogue 6H were retrieved. SCHEMBL15675695 (PubCid: 15739209) and AKOS019005527 (PubCid: 80442147) similar to Vorinostat and 6H, were the best docked compounds among the virtually screened compounds. However, in spite of having good affinity, none of the virtually screened compounds had better affinity than that of 6H. In addition SCHEMBL15675695 was predicted to be a carcinogen while AKOS019005527 is Ames toxic. From, our extensive analysis involving binding affinity analysis, ADMET properties predictions and pharmacophoric mappings, we report Vorinostat hydroxamate analogue 6H to be a potential candidate for HDAC inhibition in treatment of cancers through an epigenetic strategy.
Molecular descriptors derived from 3-D Morse and Radial Distribution Function indices were found to be selective in all the models. These molecular descriptors which encode common SAR among Vorinostat derivatives were evaluated for their potent HDAC inhibition activity.
Background: Deficits in cholinergic neurotransmission due to the degeneration of cholinergic neurons in the brain are believed to be one of the major causes of the memory impairments associated with AD. Targeting acetyl cholinesterase (AChE) surfaced as a potential therapeutic target in the treatment of Alzheimer’s disease. The present study is pursued to develop quantitative structure activity relationship (QSAR) models to determine chemical descriptors responsible for AChE activity.Methods: Two different sets of AChE inhibitors, dataset-I (30 compounds) and dataset-II (20 compounds) were investigated through MLR aided linear and SVM aided non-linear QSAR models.Results: The obtained QSAR models were found statistically fit, stable and predictive on validation scales. These QSAR models were further investigated for their common structure-activity relationship in terms of overlapping molecular descriptors selection. Atomic mass weighted 3D Morse descriptors (MATS5m) and Radial Distribution Function (RDF045m) descriptors were found in common SAR for both the datasets. Electronegativity weighted (MATS5e, HATSe, and Mor17e) descriptors have also been identified in regulative roles towards endpoint values of dataset-I and dataset-II.Conclusion: The common SAR identified in these linear and non-linear QSAR models could be utilized to design novel inhibitors of AChE with improved biological activity.
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