Current Pharmaceutical Design - Volume 22, Issue 33, 2016

In this work we report the first attempt to study the effect of activity cliffs over the generalization ability of machine learning (ML) based QSAR classifiers, using as study case a previously reported diverse and noisy dataset focused on drug induced liver injury (DILI) and more than 40 ML classification algorithms. Here, the hypothesis of structure-activity relationship (SAR) continuity restoration by activity cliffs removal is te Read More

Background: Chronic myelogenous leukemia is associated with hematopoietic stem cells that are manifested primarily with expansion myelopoiesis. It is the first cancer directly associated with a genetic abnormality. Specifically, it is associated to a particular cytogenetic abnormality, known as Philadelphia chromosome (Ph), which results from a fusion between part of the BCR (“breakpoint cluster region”) gene from chromoso Read More

Background: The Ribonuclease III (RNase III) enzymatic class is involved in many important biological processes from bacteria to higher eukaryotes. Consequently, they have been useful as drug-target candidates for drug development. Despite their high molecular diversity, RNases III share common structural and catalytic features and some degree of enzymatic activity. However, the role of accessory domains as key deter Read More

Background: Dysregulation of HDACs has been associated with tumour development and therefore inhibiting HDAC’s have surfaced as promising therapeutic strategy in malignancy. Methods: Vorinostat analogues with different biological activities were investigated for underlying structure-activity relationship. Results: Out of six activities and their multiple QSAR models, HDAC1 and HDAC8 produced statistically fit, stable and Read More

Background: The emergence of reduced susceptibility to fluoroquinolones among Salmonella enterica serotype Typhimurium isolates leading to clinical failure of treatment poses a great therapeutic challenge. Methods: The current study is focused on the evaluation of the minimum inhibitory concentration (MIC) of quinolones in 29 Salmonella typhimurium of 86 Salmonella spp. strains, obtained from pigs from the State of Mex Read More

Background: Many QSAR studies have been developed to predict acute toxicity over several biomarkers like Pimephales promelas, Daphnia magna and Tetrahymena pyriformis. Regardless of the progress made in this field there are still some gaps to be resolved such as the prediction of aquatic toxicity over the protozoan T. pyriformis still lack a QSAR study focused in accomplish the OECD principles. Methods: Atom-based quadra Read More

In the present study, a generalized approach for molecular structure characterization is introduced, based on the relation frequency matrix (F) representation of the molecular graph and the subsequent calculation of the corresponding discrete derivative (finite difference) over a pair of elements (atoms). In earlier publications (22- 24), an unique event, named connected subgraphs, (based on the Kier-Hall’s subgraphs) w Read More

We can combine experimental techniques like Flow Cytometry Analysis (FCA) with Chemoinformatics methods to predict the complex networks of interactions between organic compounds and targets in the immune system. In this work, we determined experimentally the values of EC50 = 17.82 μg/mL and Cytotoxicity = 20.6 % for the anti-microbial / anti-parasite drug Dermofural over Balb/C CD9 lymphocytes using flow cy Read More

It is still not clear whether intact lipid vesicles can cross the human skin. Some reports in the literature indicate that transfersomes® can cross the skin. Other reports suggest that intact liposomes cannot cross the skin. Of course, the composition of the various formulations has to be taken into consideration before making such assertions. The present review examines the use of vesicles- elastic liposomes and ethosomes- for tra Read More

Chemotherapy is one of the most frequently employed and reliable treatment options for the management of a variety of cancers. Taxanes (paclitaxel, docetaxel and cabazitaxel) are frequently prescribed to treat breast cancer, hormone refractory prostate cancer, non-small cell lung cancer and ovarian cancer. Most of the commercial products of taxanes are available as injectables, which are not patient compliant an Read More

Cariprazine (RGH-188) is a novel antipsychotic drug that exerts partial agonism of dopamine D2/D3 receptors with preferential binding to D3 receptor, antagonism of 5HT2B receptors and partial agonism of 5HT1A. Currently, cariprazine is in late-stage clinical development (phase III clinical trials) in patients with schizophrenia (S) and in patients with bipolar disorder (BD), as well as an adjunctive treatment in patients Read More

Blood hemostasis is attained with two sophisticated interconnected network systems, a coagulation cascade and a platelet activation system. Multiple inhibitors were developed to various components of both systems to prevent thrombosis-related morbid events that are of extremely high frequency in the human population. Antithrombotic inhibitors possess both positive and negative aspects. One of the essential modern r Read More