{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T04:35:07Z","timestamp":1774326907691,"version":"3.50.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T00:00:00Z","timestamp":1606435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Drug resistant bacteria have emerged, so robust methods are needed to evaluate combined activities of known antibiotics as well as new synthetic compounds as novel antimicrobial agents to treatment efficacy in severe bacterial infections. Marine natural products (MNPs) have become new strong leads in the drug discovery endeavor and an effective alternative to control infections. Herein, we report the bioassay guided fractionation of marine extracts from the sponges <jats:italic>Lendenfeldia<\/jats:italic>, <jats:italic>Ircinia<\/jats:italic>, and <jats:italic>Dysidea<\/jats:italic> that led us to identify novel compounds with antimicrobial properties. Chemical synthesis of predicted compounds and their analogs has confirmed that the proposed structures may encode novel chemical structures with promising antimicrobial activity against the medically important pathogens. Several of the synthetic analogs exhibited potent and broad spectrum <jats:italic>in vitro<\/jats:italic> antibacterial activity, especially against the Methicillin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA) (MICs to 12.5 \u03bcM), <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (MICs to 0.02 \u03bcM), <jats:italic>uropathogenic Escherichia coli<\/jats:italic> (MIC o 6.2 \u03bcM), and <jats:italic>Pseudomonas aeruginosa<\/jats:italic> (MIC to 3.1 \u03bcM). Checkerboard assay (CA) and time-kill studies (TKS) experiments analyzed with the a pharmacodynamic model, have potentials for <jats:italic>in vitro<\/jats:italic> evaluation of new and existing antimicrobials. In this study, CA and TKS were used to identify the potential benefits of an antibiotic combination (i.e., synthetic compounds, vancomycin, and rifampicin) for the treatment of MRSA and <jats:italic>M. tuberculosis<\/jats:italic> infections. CA experiments indicated that the association of compounds 1a and 2a with vancomycin and compound 3 with rifampicin combination have a synergistic effect against a MRSA and <jats:italic>M. tuberculosis<\/jats:italic> infections, respectively. Furthermore, the analysis of TKS uncovered bactericidal and time-dependent properties of the synthetic compounds that may be due to variations in hydrophobicity and mechanisms of action of the molecules tested. The results of cross-referencing antimicrobial activity, and toxicity, CA, and Time-Kill experiments establish that these synthetic compounds are promising potential leads, with a favorable therapeutic index for antimicrobial drug development.<\/jats:p>","DOI":"10.3389\/fmicb.2020.551189","type":"journal-article","created":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T07:17:51Z","timestamp":1606461471000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Pharmacodynamic Functions of Synthetic Derivatives for Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis"],"prefix":"10.3389","volume":"11","author":[{"given":"Mojdeh","family":"Dinarvand","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm P.","family":"Spain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatemeh","family":"Vafaee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2020,11,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/282615a0","article-title":"Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line.","volume":"282","author":"Aden","year":"1979","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s40121-018-0224-z","article-title":"Evidence from an in vitro study: is oxacillin plus vancomycin a better choice for heteroresistant vancomycin-intermediate Staphylococcus aureus?","volume":"8","author":"Bakthavatchalam","year":"2019","journal-title":"Infect. 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