Dataset Information

Physicochemical and Pharmacokinetic Analysis of Anacardic Acid Derivatives.

ABSTRACT: Anacardic acid (AA) and its derivatives are well-known for their therapeutic applications ranging from antitumor, antibacterial, antioxidant, anticancer, and so forth. However, their poor pharmacokinetic and safety properties create significant hurdles in the formulation of the final drug molecule. As a part of our endeavor to enhance the potential and exploration of the anticancer activities, a detailed study on the properties of selected AA derivatives was performed in this work. A comprehensive analysis of the drug-like properties of 100 naturally occurring AA derivatives was performed, and the results were compared with certain marketed anticancer drugs. The work focused on the understanding of the interplay among eight physicochemical properties. The relationships between the physicochemical properties, absorption, distribution, metabolism, and excretion attributes, and the in silico toxicity profile for the set of AA derivatives were established. The ligand efficacy of the finally scrutinized 17 AA derivatives on the basis of pharmacokinetic properties and toxicity parameters was further subjected to dock against the potential anticancer target cyclin-dependent kinase 2 (PDB ID: 1W98). In the docked complex, the ligand molecules (AA derivatives) selectively bind with the target residues, and a high binding affinity of the ligand molecules was ensured by the full fitness score using the SwissDock Web server. The BOILED-Egg model shows that out of 17 scrutinized molecules, 3 molecules exhibit gastrointestinal absorption capability and 14 molecules exhibit permeability through the blood-brain barrier penetration. The analysis can also provide some useful insights to chemists to modify the existing natural scaffolds in designing new anacardic anticancer drugs. The increased probability of success may lead to the identification of drug-like candidates with favorable safety profiles after further clinical evaluation.

SUBMITTER: Zafar F

PROVIDER: S-EPMC7098041 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Physicochemical and Pharmacokinetic Analysis of Anacardic Acid Derivatives.

Zafar Fahmina F Gupta Anjali A Thangavel Karthick K Khatana Kavita K Sani Ali Alhaji AA Ghosal Anujit A Tandon Poonam P Nishat Nahid N

ACS omega 20200313 11

Anacardic acid (AA) and its derivatives are well-known for their therapeutic applications ranging from antitumor, antibacterial, antioxidant, anticancer, and so forth. However, their poor pharmacokinetic and safety properties create significant hurdles in the formulation of the final drug molecule. As a part of our endeavor to enhance the potential and exploration of the anticancer activities, a detailed study on the properties of selected AA derivatives was performed in this work. A comprehensi ...[more]

PMID: 32226883

Similar Datasets

Project description:Objective:Over the last years, vitrification has been widely used for oocyte cryopreservation, in animals and humans; however, it frequently causes minor and major epigenetic modifications. The effect of oocyte vitrification on levels of acetylation of histone H4 at lysine 12 (AcH4K12), and histone acetyltransferase (Hat) expression, was previously assessed; however, little is known about the inhibition of Hat expression during oocyte vitrification. This study evaluated the effect of anacardic acid (AA) as a Hat inhibitor on vitrified mouse oocytes. Materials and Methods:In this experimental study, 248 mouse oocytes at metaphase II (MII) stage were divided in three experimental groups namely, fresh control oocytes (which were not affected by vitrification), frozen/thawed oocytes (vitrified) and frozen/thawed oocytes pre-treated with AA (treatment). Out of 248 oocytes, 173 oocytes were selected and from them, 84 oocytes were vitrified without AA (vitrified group) and 89 oocytes were pretreated with AA, and then vitrified (treatment group). Fresh MII mouse oocytes were used as control group. Hat expression and AcH4K12 levels were assessed by using real-time quantitative polymerase chain reaction (PCR) and immunofluoresce staining, respectively. In addition, survival rate was determined in vitrified and treatment oocytes. Results:Hat expression and AcH4K12 modification significantly increased [4.17 ± 1.27 (P≤0.001) and 97.57 ± 6.30 (P<0.001), respectively] in oocytes that were vitrified, compared to the fresh oocytes. After treatment with AA, the Hat mRNA expression and subsequently H4K12 acetylation levels were significantly reduced [0.12 ± 0.03 (P≤0.001) and 89.79 ± 3.20 (P≤0.05), respectively] in comparison to the vitrified group. However, the survival rate was not significantly different between the vitrified (90.47%) and treatment (91.01%) groups (P>0.05). Conclusion:The present study suggests that AA reduces vitrification risks caused by epigenetic modifications, but does not affect the quality of vitrification. In fact, AA as a Hat inhibitor was effective in reducing the acetylation levels of H4K12.

Dataset Information

Physicochemical and Pharmacokinetic Analysis of Anacardic Acid Derivatives.

Publications

Physicochemical and Pharmacokinetic Analysis of Anacardic Acid Derivatives.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets