Bioorganic & Medicinal Chemistry published new progress about 518-67-2. 518-67-2 belongs to bromides-buliding-blocks, auxiliary class Other Aromatic Heterocyclic,Salt,Amine,Benzene, name is Dimidium bromide, and the molecular formula is C20H18BrN3, Quality Control of 518-67-2.
Martins Alho, Miriam A. published the artcileAntiprotozoan lead discovery by aligning dry and wet screening: Prediction, synthesis, and biological assay of novel quinoxalinones, Quality Control of 518-67-2, the publication is Bioorganic & Medicinal Chemistry (2014), 22(5), 1568-1585, database is CAplus and MEDLINE.
Protozoan parasites have been one of the most significant public health problems for centuries and several human infections caused by them have massive global impact. Most of the current drugs used to treat these illnesses have been used for decades and have many limitations such as the emergence of drug resistance, severe side-effects, low-to-medium drug efficacy, administration routes, cost, etc. These drugs have been largely neglected as models for drug development because they are majorly used in countries with limited resources and as a consequence with scarce marketing possibilities. Nowadays, there is a pressing need to identify and develop new drug-based antiprotozoan therapies. In an effort to overcome this problem, the main purpose of this study is to develop a QSARs-based ensemble classifier for antiprotozoan drug-like entities from a heterogeneous compounds collection. Here, the authors use some of the TOMOCOMD-CARDD mol. descriptors and linear discriminant anal. (LDA) to derive individual linear classification functions to discriminate between antiprotozoan and non-antiprotozoan compounds as a way to enable the computational screening of virtual combinatorial datasets and/or drugs already approved. Firstly, the authors construct a wide-spectrum benchmark database comprising of 680 organic chems. with great structural variability (254 of them antiprotozoan agents and 426 to drugs having other clin. uses). This series of compounds was processed by a k-means cluster anal. to design training and predicting sets. In total, seven discriminant functions were obtained, by using the whole set of atom-based linear indexes. All the LDA-based QSAR models show accuracies above 85% in the training set and values of Matthews correlation coefficients (C) vary from 0.70 to 0.86. The external validation set shows rather-good global classifications of around 80% (92.05% for best equation). Later, the authors developed a multi-agent QSAR classification system, in which the individual QSAR outputs are the inputs of the aforementioned fusion approach. Finally, the fusion model was used for the identification of a novel generation of lead-like antiprotozoan compounds by using ligand-based virtual screening of ‘available’ small mols. (with synthetic feasibility) in the authors’ ‘inhouse’ library. A new mol. subsystem (quinoxalinones) was then theor. selected as a promising lead series, and its derivatives subsequently synthesized, structurally characterized, and exptl. assayed by using in vitro screening that took into consideration a battery of five parasite-based assays. The chems. 7-Nitro-4-(5-piperidinopentyl)-3,4-dihydro-1H-quinoxalin-2-one hydrobromide (11), 4-(5-Azepanylpentyl)-7-nitro-3,4-dihydro-1H-quinoxalin-2-one hydrobromide (12) and 1-Methyl-7-nitro-4-(5-piperidinopentyl)-3,4-dihydro-1H-quinoxalin-2-one hydrobromide (16) are the most active (hits) against apicomplexa (sporozoa) and mastigophora (flagellata) subphylum parasites, resp. Both compounds depicted good activity in every protozoan in vitro panel and they did not show unspecific cytotoxicity on the host cells. The described tech. framework seems to be a promising QSAR-classifier tool for the mol. discovery and development of novel classes of broad-antiprotozoan-spectrum drugs, which may meet the dual challenges posed by drug-resistant parasites and the rapid progression of protozoan illnesses.
Bioorganic & Medicinal Chemistry published new progress about 518-67-2. 518-67-2 belongs to bromides-buliding-blocks, auxiliary class Other Aromatic Heterocyclic,Salt,Amine,Benzene, name is Dimidium bromide, and the molecular formula is C20H18BrN3, Quality Control of 518-67-2.
Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary