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Potential toxicity due to nonspecific distribution is one of the major challenges with currently available chemotherapeutics. In the present report we have developed Docetaxel (DTX) loaded Anacardic acid (AA) functionalized liposomes (DTX-AA-PEG-Liposomes) to have the advantage of selective distribution to cancer cells due to recognition and enhanced uptake by VEGF receptors. AA dual conjugate (AA-PEG-AA) was synthesized by using carbodiimide chemistry and further used to formulate the AA functionalized DTX loaded liposomes by using film hydration method. Extensive optimization of different process variables resulted in the formation of liposomes with particle size 126.4 ± 6.2 nm and PDI 0.239 ± 0.03. The freeze dried DTX-AA-PEG-Liposomes demonstrated sustained release for up to 24 h and excellent stability at accelerated storage stability conditions. Qualitative cell uptake studies demonstrated remarkably higher cellular uptake of Coumarin-6 (C-6) loaded liposomes, while quantitative determination revealed 2.64 and 2.88-fold higher uptake of DTX-AA-PEG-Liposomes in comparison with free DTX. Cell culture studies in MCF-7 to determine cellular uptake mechanism demonstrated clathrin and caveolae mediated internalization of liposomes, independent of Organic Anion Transporting Polypeptides (OATPs) transporters. Moreover, developed liposomes demonstrated relatively higher cell inhibition and apoptosis in MCF-7 cells as compared to free DTX. Furthermore, in vivo pharmacokinetics demonstrated 3.7 and 4.5-fold increase in AUC and t 1/2 value of DTX-AA-PEG-Liposomes as compared to Taxotere ® , respectively. Moreover, DTX-AA-PEG-Liposomes demonstrated significant reduction in tumor volume and toxicity in comparison with marketed formulation (Taxotere ® ), confirming enhanced efficacy and safety of the developed formulation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Histone deacetylase inhibitors (HDACi) have been demonstrated as an emerging class of anticancer drugs involved in regulation of gene expression and chromatin remodeling thus indicating valid targets for different types of cancer therapeutics. The pan-deacetylase inhibitor panobinostat (Farydac®, LBH589) is developed by Novartis Pharmaceuticals and a newly US FDA approved drug for the multiple myeloma. It is under clinical investigation for a range of hematological and solid tumors worldwide in both oral and intravenous formulations. Panobinostat inhibits tumor cell growth by interacting with acetylation of histones and nonhistone proteins as well as various apoptotic, autophagy-mediated targets and various tumorigenesis pathways involved in the development of cancer. The current article summarizes the status of panobinostat in gastrointestinal cancers. Preclinical and clinical data suggest that panobinostat has potential inhibitory activity in hepatocellular, pancreatic, colorectal, gastric and gastrointestinal stromal tumors. Clinical evaluations of panobinostat are currently underway. Herein, we have also reviewed the rationale behind the combination therapy under the trials and possible future prospective for the treatment of GI tumors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Histone deacetylase (HDAC) inhibitors can reactivate gene expression and inhibit the growth and survival of cancer cells., Objective: To identify the important pharmacophoric features and correlate 3Dchemical structure with biological activity using 3D-QSAR and Pharmacophore modeling studies., Method: The pharmacophore hypotheses were developed using e-pharmacophore script and phase module. Pharmacophore hypothesis represents the 3D arrangement of molecular features necessary for activity. A series of 55 compounds with wellassigned HDAC inhibitory activity were used for 3D-QSAR model development., Results: Best 3D-QSAR model, which is a five partial least square (PLS) factor model with good statistics and predictive ability, acquired Q2 (0.7293), R2 (0.9811), cross-validated coefficient rcv 2=0.9807 and R2 pred=0.7147 with low standard deviation (0.0952). Additionally, the selected pharmacophore model DDRRR.419 was used as a 3D query for virtual screening against the ZINC database. In the virtual screening workflow, docking studies (HTVS, SP and XP) were carried out by selecting multiple receptors (PDB ID: 1T69, 1T64, 4LXZ, 4LY1, 3MAX, 2VQQ, 3C10, 1W22). Finally, six compounds were obtained based on high scoring function (dock score -11.2278-10.2222 kcal/mol) and diverse structures., Conclusion: The structure activity correlation was established using virtual screening, docking, energetic based pharmacophore modelling, pharmacophore, atom based 3D QSAR models and their validation. The outcomes of these studies could be further employed for the design of novel HDAC inhibitors for anticancer activity.