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Current Computer-aided Drug Design

Balazs Balogh, Anna Carbone, Virginia Spanò, Alessandra Montalbano, Paola Barraja, Stella Cascioferro, Patrizia Diana, Barbara Parrino
BACKGROUND: Isoindolo[2,1-a]quinoxalines constitute an important class of compounds which demonstrated potent antiproliferative activity against different human tumor cell lines and topoisomerase I inhibition. In particular, their water soluble imine or iminium salts recently synthesized, showed potent growth inhibitory effect on NCI-60 tumor cell line panel and biological studies performed on the most active compounds demonstrated that they cause DNA damage via topoisomerase I poisoning...
January 23, 2017: Current Computer-aided Drug Design
Elnaz Habibpour, Shahin Ahmadi
BACKGROUND: The health and life of humans have been seriously threatened by cancer for a long period and cancer has become the leading disease-related cause of deaths of human population. Natural products such as colchicine and vinblastine inhibit microtubule assembly by preventing tubulin polymerization. GA-MLR is a powerful search technique based on the evolution of biological systems for QSAR modeling. In this paper, we studied QSAR modeling of some arylthioindole class of colchicine polymerization inhibitors as anticancer agents using GA-MLR and stepwise-MLR...
January 23, 2017: Current Computer-aided Drug Design
Ibezim Akachukwu, Olujide Oludayo Olubiyi, Ata Kosisochukwu, Mbah Chika John, Nwodo Ngozi Justina
: Background Schistosomiasis is a parasitic protozoal disease caused by flatworms of the genus Schistosoma. Although the disease threatens millions of lives, it is still at the top list of neglected tropical diseases and praziquantel, the only common schistosocidal drug in use, has records of decreasing efficiency and cases of resistance. Also, reports revealed that people in the rural areas, who are most affected, rely mostly on traditional herbal medicines because of limited access to modern healthcare...
January 19, 2017: Current Computer-aided Drug Design
Vangala Radhika, Hassan Araimsh Jaraf, Sivan Sree Kanth, Manga Vijjulatha
BACKGROUND: The accuracy of molecular conformation for Quantitative Structure Activity Relationship (QSAR) studies is an important criteria, and the most favourable bioactive conformer selection is a tough task. Correct ligand alignment as input for 3D-QSAR is an important step that is prone to human biases. Multiple-dimensional QSAR (mQSAR) approach provides a promising alternative to classic 3D-QSAR for drug discovery purposes. OBJECTIVE: Obtaining ligand conformations from multiple receptor conformation docking (MRCD) will reduce the margin of error by incorporating the receptor based alignment of ligand conformations...
January 19, 2017: Current Computer-aided Drug Design
Mucheli Ramana, Rama Lokhande, Shanta Bhar, Prasanna Ranade, Ankita Mehta, Gayatri Gadre
BACKGROUND: Breast cancer is a systemic disease which has challenged physicians worldwide as it is the most predominant cancer in women often leading to fatality. One of the types of treatment is chemotherapy which includes targeted oral or intravenous cancer-killing drugs. Treatment options are often limited to surgery and/or chemotherapy. OBJECTIVE: The discovery and design of new small molecule estrogen inhibitors is necessitated in order to circumvent the problem of drug-induced resistance in chemotherapy resulting in disease relapse...
December 23, 2016: Current Computer-aided Drug Design
Heena R Bhojwani, Urmila J Joshi
BACKGROUND: Kinase domain of VEGFR-2 displays conformational flexibility which leads to existence of two kinds of inhibitors viz. type I and type II inhibitors. They exhibit different binding modes and this necessitates the development of separate pharmacophore models for them. METHODS: The virtual screening study for discovery of type I inhibitors of VEGFR-2 kinase was done by using combined pharmacophore (generated using PHASE and validated by 3D-QSAR) and docking (Glide) based approach...
December 14, 2016: Current Computer-aided Drug Design
SeeKhai Lim, Rozana Othman, Rohana Yusof, ChoonHan Heh
BACKGROUND: Hepatitis C is a significant cause for end-stage liver diseases and liver transplantation which affects approximate 3% of the global populations. Despite the present of several direct antiviral agents in the treatment of hepatitis C, the standard treatment for HCV is accompanied by several drawbacks such as adverse side effects, high pricing of medications and the rapid emerging rate of resistant HCV variants. OBJECTIVES: To discover potential inhibitors for HCV helicase through an optimized in silico approach...
November 30, 2016: Current Computer-aided Drug Design
Vytautas Raskevicius, Visvaldas Kairys
BACKGROUND: Design of isoform-specific inhibitors is a major challenge in the new therapeutic agents development. METHODS: The article describes the development of a robust selectivity for CA XII QSAR and 3DQSAR models of 40 benzenesulfonamide derivatives bearing pyrimidine moieties using PHASE module of Schrödinger for 3D-QSAR or E-DRAGON and R software for 2D-QSAR. Two QSAR protocols were explored: traditional (affinity) and selectivity (affinity ratio) based...
November 29, 2016: Current Computer-aided Drug Design
Arbind Kumar, Pratibha Maan, Gurpreet Singh, Jagdeep Kaur
BACKGROUND: Death toll due to tuberculosis is still rising day by day. Whole genome sequence of Mycobacterium tuberculosis has provided a platform to conduct research in order to identify the probable drug target. OBJECTIVES: Out of 4000 gene products of M. tuberculosis, approximately 40% of proteins are annotated as hypothetical. Identifying and characterizing these proteins could provide a new prescriptive for developing new TB drugs. Rv1288, a protein of M. tuberculosis H37Rv has been annotated as a hypothetical protein in database...
November 24, 2016: Current Computer-aided Drug Design
Kłosińska-Szmurło Ewa, Mazurek Aleksander Paweł, Grudzień Monika, Betlejewska-Kielak Katarzyna
BACKGROUND: Two main factors, which have an influence on oral absorption from solid, immediate release dosage form, are solubility and permeability. These are considered the main fundamental properties that govern the rate and extent of oral absorption. The significance of these properties has been highlighted in the Biopharmaceutics Classification System (BCS). OBJECTIVE: The concept of this paper was to predict the solubility and permeability of fluoroquinolones using in silico methods based on the assumptions of the BCS...
October 14, 2016: Current Computer-aided Drug Design
Kunal Zaveri, Kiranmayi Patnala
BACKGROUND: The prevalence of multi-drug resistance S. aureus is one most challenging task for treatment of nosocomial infections. Proteins and enzymes of peptidoglycan biosynthesis pathway are one among the well-studied targets, but many of the enzymes are unexplored as targets. MurE is one such enzyme featured to be a promising target. As MurE plays an important role in ligating the L-lys to stem peptide at third position that is crucial for peptidoglycan synthesis. OBJECTIVE: To screen the potential MurE inhibitor...
October 10, 2016: Current Computer-aided Drug Design
Mircea V Diudea, Beata Szefler, Przemysław Czeleń
BACKGROUND: Indolizines represent a class of heteroaromatic compounds, of pharmacological importance, containing two condensed 5- and 6-memebered rings bridged by a nitrogen atom. Despite indolizine is an important medicinal moiety, a detailed view on the mechanism of action of biologically active indolizines is unavailable. OBJECTIVE: The study of ligand-enzyme affinity is of high interest; description of characteristics (energetic and geometric ones) of ligand binding to the active sites of an enzyme could be useful in understanding the action mechanism of a given ligand on the concerned enzyme...
October 4, 2016: Current Computer-aided Drug Design
Nidhi Rani Prajapat, Randhir Singh
Molecular docking study has become a standard tool for the investigation of drug- receptor interaction. In the present study 18 new imidazole derivatives having mercapto group (4a-r) were synthesized. Structures of the newly synthesized compounds were characterized by spectral studies. Compounds were screened for their antimicrobial potency. Compounds 4j and 4k were found to be the most potent compounds of the series against al the tested strains with MIC ranging from 2-8µg/ml. All the compounds were subjected to molecular docking studies for the inhibition of the enzyme 14α-demethylase...
September 15, 2016: Current Computer-aided Drug Design
Olujide Oludayo Olubiyi, Maryam O Olagunju, Abiola O Obisesan
The metabolic action of CYP2D6 remains a crucial factor influencing the therapeutic outcomes for some drug molecules while others are largely or only slightly affected. To understand the basis for the metabolic discrimination, the structural and physicochemical details of its interaction with established drug substrates were investigated at atomistic resolution. The otherwise relatively extensive binding surface was found to present subtle but important topological features that explain the enzyme's highly efficient capability for processing diverse chemical classes of drugs and endogenous substrates...
September 8, 2016: Current Computer-aided Drug Design
Sajjad Ahrari, Fatemeh Dabbagh, Sobhan Ahrari, Younes Ghasemi, Navid Mogharrab, Yasser Riazalhosseini
BACKGROUND: Urate oxidase is absent in humans so the enzyme is considered as an important therapeutic agent to control hyperuricemic disorders. Currently available enzymes with pharmaceutical applications have adverse effects associated with allergic reactions and anaphylactic shocks, in case of chronic treatment. Therefore, developing variant forms of the enzyme, with lower immunogenicity and similar or higher activity, is of great importance. AIM: Here, we tried to improve the structure of a recently resurrected ancestral mammalian urate oxidase (which is claimed to have higher enzymatic activity compared to other mammalian counterparts) by introducing eight rational mutations and verified the consequence of these mutations on immunogenicity, stability and the affinity of protein to uric acid by computational techniques...
September 5, 2016: Current Computer-aided Drug Design
Lemont B Kier
Our previous studies of the role of proton hopping in nerve conduction have dealt with the axon, soma, synapse, and nodes of Ranvier. We complete the study and application of the theory of proton hopping being the system of nerve conduction by examining the dendrites and their accompanying spines as they function within the nerve system. The role of proton hopping continues to be a very probable mechanism within this intermediate system linking two nerves at the synapse.
July 25, 2016: Current Computer-aided Drug Design
Noelly Madeleine, Fabrice Gardebien
Ahead of Print article withdrawn by publisher
July 18, 2016: Current Computer-aided Drug Design
Roopa Lalitha, Pravin Kumar, Sudheer Mohammed
Mutant actins D157E and R183A-D184A are reported to resist the anticancer drug Latrunculin A (LAT); though identified, the mechanism of resistance is not clearly understood. To design a better molecule that can overcome the resistance caused by mutations it is important to define precise pharmacophoric regions in LAT based on the mechanism of resistance on the mutant actin -LAT interactions. To address this we have conducted 20 nano seconds (ns) simulation of mutant actins - LAT complex and compared it with the 20ns simulation of wild actin - LAT complex...
May 5, 2016: Current Computer-aided Drug Design
Shabana Bibi, Katsumi Sakata
BACKGROUND: Diabetes is a metabolic disorder that requires multiple therapeutic approaches. The pancreas loses its functionality to properly produce the insulin hormone in patients with diabetes mellitus. In 2012, more than one million people worldwide died as a result of diabetes, which was the eighth leading cause of death. OBJECTIVE: Most drugs currently available and approved by the U.S. Food and Drug Administration cannot reach an adequate level of glycemic control in diabetic patients, and have many side effects; thus, new classes of compounds are required...
April 26, 2016: Current Computer-aided Drug Design
Gizem Tatar, Tugba Taskin Tok
The coronavirus nucleocapsid (N) plays an important role in the virus structure, the replication, and the transcription of CoV. This protein, which has a helix and flexible structure, and capable of binding on to the viral genomic RNA, is a non-structural protein (nsp3). Many studies suggest that the N protein interaction with nsp3 plays a critical role in the virus replication early in infection. Therefore, it is necessary to know the definition of the interaction mechanism of N and nsp3 protein in terms of the CoV replication transcription mechanism...
February 26, 2016: Current Computer-aided Drug Design
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