ABSTRACT
Here we described a natural product inspired modular DOS strategy for the synthesis of a library of hybrid systems that are structurally and stereochemically disparate. The main scaffold is a pyrroloisoquinoline motif, that is synthesized from tandem Pictet-Spengler lactamization. The structural diversity is generated via "privileged scaffolds" that are attached at the appropriate site of the motif. Screening of the library compounds for their antiplasmodial activity against chloroquine sensitive 3D7 cells indicated few compounds with moderate activity (20-50 µM). A systematic comparison of structural intricacy between the library members and a natural product dataset obtained from ZINC(®) revealed comparable complexity.
Subject(s)
Antimalarials/pharmacology , Biological Products/pharmacology , Erythrocytes/drug effects , Malaria/drug therapy , Plasmodium falciparum/drug effects , Small Molecule Libraries/pharmacology , Antimalarials/chemistry , Cells, Cultured , Combinatorial Chemistry Techniques , Drug Discovery , Humans , Malaria/parasitology , Molecular Structure , Plasmodium falciparum/growth & development , Structure-Activity Relationship , Trophozoites/drug effectsABSTRACT
In this overview, we examine recent developments in network approaches to drug design. A brief overview of networks is followed by a discussion of how chemical similarity networks and their properties address challenges in drug design. Multiple methods used to assess or enhance chemical diversity for early-stage drug discovery are discussed, as well as methods that can be used for drug repositioning and ligand polypharmacology.
Subject(s)
Drug Discovery/economics , Drug Discovery/methods , Proteins/chemistry , Small Molecule Libraries , Drug Design , Models, Molecular , Molecular Docking Simulation , Quantitative Structure-Activity Relationship , SoftwareABSTRACT
PURPOSE: There is limited work analyzing the efficacy of different antiseptics in reducing wound contamination by the skin flora during hernia repair and its influence on the incidence of wound infection, which continues to be a major problem in the developing world. This study was designed to test if chlorhexidine-ethanol has superior antimicrobial efficacy compared with povidone-iodine. METHODS: In a prospective randomized trial, the efficacy of chlorhexidine-ethanol and povidone-iodine in the reduction of colony counts of the skin flora and the incidence of surgical site infection was compared. RESULTS: Both povidone-iodine and chlorhexidine-ethanol produced significant reduction in the skin bacterial colony counts, from 18.66 x 10(2) to 2.34 x 10(2) colony-forming units with povidone-iodine (59%) and from 12.34 x 10(2) to 0.93 x 10(2) colony-forming units (82%) with chlorhexidine-ethanol. Infection rates with the use of povidone-iodine and chlorhexidine-ethanol groups were not significantly different (9.5 vs. 7.0; p = 0.364). The reduction in colony counts in those who developed infection was only 15.6% compared with 77.1% in those who did not develop infection. CONCLUSIONS: The antibacterial efficacy of chlorhexidine-ethanol and povidone-iodine is comparable in open hernia repair.
Subject(s)
Anti-Infective Agents, Local/therapeutic use , Chlorhexidine/therapeutic use , Ethanol/therapeutic use , Herniorrhaphy , Povidone-Iodine/therapeutic use , Skin/microbiology , Surgical Wound Infection/prevention & control , Adult , Anti-Infective Agents, Local/administration & dosage , Chlorhexidine/administration & dosage , Colony Count, Microbial , Ethanol/administration & dosage , Female , Hernia/complications , Humans , Male , Middle Aged , Povidone-Iodine/administration & dosageABSTRACT
Urea and thiourea derivatives of oxazolidinones were synthesized and their inhibitory activity (MIC) was determined on the bacterial strains which includes clinical isolates and quality control organisms. The structure activity relationships were studied and a 3D-QSAR model was built using Genetic Function Approximation. Interestingly found that electron withdrawing groups at the ortho position of the phenyl ring enhances the activity.
