Department of Computer Science, School of Computing, Tokyo Institute of Technology, 4259-J3-23, Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan. Electronic address:
Published: August 2021
AI Article Synopsis
Article Abstract
Neglected tropical diseases (NTDs) are parasitic and bacterial infections that are widespread, especially in the tropics, and cause health problems for about one billion people over 149 countries worldwide. However, in terms of therapeutic agents, for example, nifurtimox and benznidazole were developed in the 1960s to treat Chagas disease, but new drugs are desirable because of their side effects. Drug discovery takes 12 to 14 years and costs $2.6 billon dollars, and hence, computer aided drug discovery (CADD) technology is expected to reduce the time and cost. This paper describes our methods and results based on CADD, mainly for NTDs. An overview of databases, molecular simulation and pharmacophore modeling, contest-based drug discovery, and machine learning and their results are presented herein.
Department of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
DNA interstrand cross-links (ICLs) are the sources of the cytotoxicity of many anticancer agents. Selenium compounds showed great potential as anticancer drugs. In this work, we synthesized a binaphthalene analog containing phenyl selenide (-SePh) as the leaving group and investigated its photochemical reactivity toward DNA as well as its cytotoxicity and selectivity.
The increasing occurrence of infections caused by multidrug-resistant (MDR) bacteria drives the need for new antibacterial drugs. Due to the current lack of antibiotic discovery and development, new strategies to fight MDR bacteria are urgently needed. Efforts to develop new antibiotic adjuvants to increase the effectiveness of existing antibiotics and design delivery systems are essential to address this issue.
Promoting tumor cell senescence arrests the cell cycle of tumor cells and activates the immune system to eliminate these senescent cells, thereby suppressing tumor growth. Nevertheless, PD-L1 positive senescent tumor cells resist immune clearance and possess the ability to secret various cytokines and inflammatory factors that stimulate the growth of tumor cells. Consequently, drugs capable of both triggering senescence in tumor cells and concurrently diminishing the expression of PD-L1 to counteract immune evasion are urgently needed.
Pulmonary fibrosis (PF) is a progressive, fatal lung disease lacking effective treatments. Autotaxin (ATX) plays a crucial role in exacerbating inflammation and fibrosis, making it a promising target for fibrosis therapies. Herein, starting from PAT-409 (Cudetaxestat), a series of novel ATX inhibitors bearing 1-indole-3-carboxamide, 4,5,6,7-tetrahydro-7-pyrazolo[3,4-]pyridin-7-one, or 4,5,6,7-tetrahydro-1-pyrazolo[4,3-]pyridine cores were designed based on the structure of ATX hydrophobic tunnel.
Antimicrobial resistance is a significant cause of mortality globally due to infections, a trend that is expected to continue to rise. As existing treatments fail and new drug discovery slows, the urgency to develop novel antimicrobial therapeutics grows stronger. One promising strategy involves targeting bacterial systems exclusive to pathogens, such as the transcription regulator protein GabR.
