Dataset Information

Design, Biological Evaluation, and Computer-Aided Analysis of Dihydrothiazepines as Selective Antichlamydial Agents.

ABSTRACT: Chlamydia trachomatis (CT) causes the most prevalent sexually transmitted bacterial disease in the United States. The lack of drug selectivity is one of the main challenges of the current antichlamydial pharmacotherapy. The metabolic needs of CT are controlled, among others, by cylindrical proteases and their chaperones (e.g., ClpX). It has been shown that dihydrothiazepines can disrupt CT-ClpXP. Based on this precedent, we synthesized a dihydrothiazepine library and characterized its antichlamydial activity using a modified semi-high-throughput screening assay. Then, we demonstrated their ability to inhibit ClpX ATPase activity in vitro, supporting ClpX as a target. Further, our lead compound displayed a promising selectivity profile against CT, acceptable cytotoxicity, no mutagenic potential, and good in vitro stability. A two-dimensional quantitative structure-activity relationship (2D QSAR) model was generated as a support tool in the identification of more potent antichlamydial molecules. This study suggests dihydrothiazepines are a promising starting point for the development of new and selective antichlamydial drugs.

SUBMITTER: de Campos LJ

PROVIDER: S-EPMC10056257 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Design, Biological Evaluation, and Computer-Aided Analysis of Dihydrothiazepines as Selective Antichlamydial Agents.

de Campos Luana Janaína LJ Seleem Mohamed A MA Feng Jiachen J Pires de Oliveira Kelly Mari KM de Andrade Dos Santos João Víctor JV Hayer Shivdeep S Clayton Jonathan B JB Kathi Sharvath S Fisher Derek J DJ Ouellette Scot P SP Conda-Sheridan Martin M

Journal of medicinal chemistry 20230125 3

<i>Chlamydia trachomatis</i> (CT) causes the most prevalent sexually transmitted bacterial disease in the United States. The lack of drug selectivity is one of the main challenges of the current antichlamydial pharmacotherapy. The metabolic needs of CT are controlled, among others, by cylindrical proteases and their chaperones (<i>e.g.</i>, ClpX). It has been shown that dihydrothiazepines can disrupt CT-ClpXP. Based on this precedent, we synthesized a dihydrothiazepine library and characterized ...[more]

PMID: 36696579

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Project description:Concerns associated with the assessment of aesthetic damage or injury raise critical difficulties, such as the scarcity of methodology and standardization that may result in fundamental precepts to establish impartial forms of compensation and aiming the total reparation of bodily injury. The complexity of the aesthetic damage evaluation is associated with the confluence of legal and technical perspectives and expert subjectivity while conducting examination and writing a report. Experts face additional difficulties associated with the objectivity while assessing aesthetic damage, independently on its location or expert skills, due to complex details observed in these lesions. Another situation in the clinical area, doctors (mainly plastic surgeons) and dentists could show the improvement or not, of the aesthetic condition to the patients. In health related areas, the use of information technology has contributed to increase the number of appropriate diagnoses, besides promoting quality, efficiency and satisfaction to health care providers. In order to make this assessment more objective, a technological tool was developed to aid experts in the evaluation of aesthetic damage and report elaboration. The objective was to develop computer-aided design software for aesthetic damage quantification/evaluation that is accessible via internet to be applied as a complementary report on body aesthetic damage. The software uses as a parameter the AIPE method, translated transculturally from Spanish to Portuguese and English. The present study allowed the construction of open access auxiliary software for the evaluation of corporal aesthetic damage. Its use is facilitated by intuitive and interactive filling, and the text may be customized by the user. It transforms the report into PDF and saves all evaluations already done in its own file. Information is encrypted for added security and confidentiality. The software is available on website at https://www.aestheticdamage.com.

Dataset Information

Design, Biological Evaluation, and Computer-Aided Analysis of Dihydrothiazepines as Selective Antichlamydial Agents.

Publications

Design, Biological Evaluation, and Computer-Aided Analysis of Dihydrothiazepines as Selective Antichlamydial Agents.

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