Antibiotic natural product hunanamycin A: Lead identification towards anti-Salmonella agents

  • Eur J Med Chem. 2022 Jun 5;236:114245. doi: 10.1016/j.ejmech.2022.114245.
Rahul D Shingare  1 ,  John B MacMillan  2 ,  D Srinivasa Reddy  3
Affiliations
  • 1. CSIR-National Chemical Laboratory, Division of Organic Chemistry, Dr. HomiBhabha Road, Pune, 411008, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110 025, India.
  • 2. Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390, United States; Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA, 95064, United States. Electronic address: [email protected].
  • 3. CSIR-National Chemical Laboratory, Division of Organic Chemistry, Dr. HomiBhabha Road, Pune, 411008, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110 025, India; Natural Products & Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India. Electronic address: [email protected].
PMID: 35421661 DOI: 10.1016/j.ejmech.2022.114245
Abstract

Design and synthesis of library of compounds around the Antibiotic natural product hunanamycin A scaffold and their biological evaluation are disclosed here. These efforts resulted in identification of a lead compound 36, which is a structurally simplified analogue of original hunanamycin A with impressive activity against Salmonella enterica and possesses Other druggable properties. In addition, no acute oral toxicity was observed for compound 36 in Swiss albino mice dosed up to 2 g/kg. It has the potential to be developed for the treatment of food infections caused by Salmonella.

Keywords
Antibiotic natural product; Hunanamycin A; Riboflavin synthase; Salmonella; Structure activity relationship.
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