Background:
Human Epidermal development factor Receptor-2 (HER2) is a membrane
tyrosine kinase which is overexpressed and gene amplified in human breast cancers. HER2 amplification
and overexpression have been linked to important tumor cell proliferation and survival pathways
for 20% of instances of breast cancer. 9-aminoacridines are significant DNA-intercalating
agents because of their antiproliferative properties.
Objective:
Some novel isoxazole substituted 9-anilinoacridines(1a-z) were designed by in-silico
technique for their HER2 inhibitory activity. Docking investigations of compounds 1a-z are performed
against HER2 (PDB id-3PP0) by using Schrodinger suit 2016-2.
Methods:
Molecular docking study for the designed molecules 1a-z are performed by Glide module,
in-silico ADMET screening by QikProp module and binding free energy by Prime-MMGBSA module
of Schrodinger suit. The binding affinity of designed molecules 1a-z towards HER2 was chosen
based on GLIDE score.
Results:
Many compounds showed good hydrophobic communications and hydrogen bonding associations
to hinder HER2. The compounds 1a-z, aside from 1z have significant Glide scores in the
scope of - 4.91 to - 10.59 when compared with the standard Ethacridine (- 4.23) and Tamoxifen
(- 3.78). The in-silico ADMET properties are inside the suggested about drug likeness. MM-GBSA
binding of the most intense inhibitor is positive.
Conclusion:
The outcomes reveal that this study provides evidence for the consideration of isoxazole
substituted 9-aminoacridine derivatives as potential HER2 inhibitors. The compounds,
1s,x,v,a,j,r with significant Glide scores may produce significant anti breast cancer activity and further
in vitro and in vivo investigations may prove their therapeutic potential.
ABSTRACT. The study focused on the molecular docking of GC-MS isolated compounds from the Sargassum wightii against inflammatory marker Cycloxigenase-2 (COX2). Seven compounds isolated by GC-MS were tested for their anti-inflammatory action using insilico analysis. The crystal structure obtained from the protein data bank was docked against seven compounds and the glide score as well as glide energy were determined using Schrödinger Maestro software (version 2013.1). The results of molecular docking showed that out of the seven bioactive compounds tested, methyl salicylate, benzoic acid, 2-hydroxy-,ethyl ester, diethyl phthalate, hexadecanoic acid, ethyl ester and (E) -9-octadecenoic acid ethyl ester were effectively inhibited the COX2 protein. The ADME properties of the compounds analyzed using Qikprop version 3.6 software of Schrodinger suite and the results showed that all the compounds were biologically active and the scores were within the acceptable range. This study revealed that the possibility of using these compounds against COX2 to treat inflammation.
Constipation is a frequent cause of distress in advanced cancer. A palliative care unit in Kerala, a southern state of India, conducted a controlled trial comparing a liquid Ayurvedic (herbal) preparation (Misrakasneham) with a conventional laxative tablet (Sofsena) in the management of opioid-induced constipation in patients with advanced cancer. Although there was no statistically significant difference in the apparent degree of laxative action between the two, the results indicate that the small volume of the drug required for effective laxative action, the tolerable taste, the once-daily dose, the acceptable side effect profile, and the low cost make Misrakasneham a good choice for prophylaxis in opioid-induced constipation. There is a need for further studies of Ayurvedic medicines in palliative care.
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