Toxicity prediction and analysis of flavonoid apigenin as a histone deacetylase inhibitor: an in-silico approach.

Occurrence of cancer is driving up on a global scale that exerts greater implications on the physical, psychological and economic stability of the human population. In the present context, numerous research studies are being conducted to explore and discover the drug molecule as an anticancer agent. Diverse scales of flavonoids entail the human diet, and they displayed prospective curative effects against an array of ailments. Among different categories of flavonoids, apigenin a trihydroxy flavone has been proven to have various pharmacological effects. Molecular docking is a key tool in structural molecular biology and computer assisted drug design. In this study, HDAC inhibitory action of apigenin and its probable toxicity was assessed by docking study using Auto dock platform. Molecular dynamics simulation was done by using iMODS server for elucidating the stability of the receptor-ligand complex. Toxicity predictions were evaluated by using tools such as CarcinoPred for carcinogenicity study, pkCSM for ADMET analysis, ProTox-II for rodent oral toxicity, lazar for estimating mutagenicity, BOILED Egg plot analysis for examining the gastrointestinal absorption and blood brain permeability, PASS prediction to identify the various biological functions and DruLiTo program to compute the drug likeness property.

Antineoplastic activity of plant-derived compounds mediated through inhibition of histone deacetylase: a review.

In the combat of treating cancer recent therapeutic approaches are focused towards enzymatic targets as they occupy a pivotal participation in the cascade of oncogenesis and malignancy. There are several enzymes that modulate the epigenetic pathways and chromatin structure related to cancer mutation. Among several epigenetic mechanisms such as methylation, phosphorylation, and sumoylation, acetylation status of histones is crucial and is governed by counteracting enzymes like histone acetyl transferase (HAT) and histone deacetylases (HDAC) which have contradictory effects on the histone acetylation. HDAC inhibition induces chromatin relaxation which forms euchromatin and thereby initiates the expression of certain transcription factors attributed with apoptosis, which are mostly correlated with the expression of the p21 gene and acetylation of H3 and H4 histones. Most of the synthetic and natural HDAC inhibitors elicit antineoplastic effect through activation of various apoptotic pathways and promoting cell cycle arrest at various phases. Due to their promising chemo preventive action and low cytotoxicity against normal host cells, bioactive substances like flavonoids, alkaloids, and polyphenolic compounds from plants have recently gained importance. Even though all bioactive compounds mentioned have an HDAC inhibitory action, some of them have a direct effect and others enhance the effects of the standard well known HDAC inhibitors. In this review, the action of plant derived compounds against histone deacetylases in a variety of in vitro cancer cell lines and in vivo animal models are articulated.