New antibiotics are urgently needed to address increasing rates of multidrug resistant infections. Seventy-six diversely functionalized compounds, comprising five structural scaffolds, were synthesized and tested for their ability to inhibit microbial growth. Twenty-six compounds showed activity in the primary phenotypic screen at the Community for Open Antimicrobial Drug Discovery (CO-ADD). Follow-up testing of active molecules confirmed that two unnatural dipeptides inhibit the growth of Cryptococcus neoformans with a minimum inhibitory concentration (MIC) ≤ 8 μg/mL. Syntheses were carried out by undergraduate students at five schools implementing Distributed Drug Discovery (D3) programs. This report showcases that a collaborative research and educational process is a powerful approach to discover new molecules inhibiting microbial growth. Educational gains for students engaged in this project are highlighted in parallel to the research advances. Aspects of D3 that contribute to its success, including an emphasis on reproducibility of procedures, are discussed to underscore the power of this approach to solve important research problems and to inform other coupled chemical biology research and teaching endeavors.

中文翻译：

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多机构研究和教育合作确定了新的抗菌化合物

迫切需要新的抗生素来解决日益增长的多重耐药性感染。合成了包括五个结构支架的76种不同功能的化合物，并测试了它们抑制微生物生长的能力。26种化合物在开放式抗菌药物发现社区（CO-ADD）的主要表型筛选中显示出活性。活性分子的后续测试证实了两种非天然二肽抑制了新型隐球菌的生长最小抑菌浓度（MIC）≤8μg/ mL。由实施分布式药物发现（D3）计划的五所学校的本科生进行了合成。该报告表明，协作研究和教育过程是发现抑制微生物生长的新分子的有力方法。在研究进展的同时，着重强调了参与该项目的学生的教育收益。讨论了D3有助于其成功的各个方面，包括强调程序的可重复性，以强调该方法解决重要研究问题并为其他结合的化学生物学研究和教学工作提供帮助的力量。