Design and synthesis of 2-amino-thiophene-tethered ureidopenicillin analogs with potentantibacterial and antitubercular activity

TitleDesign and synthesis of 2-amino-thiophene-tethered ureidopenicillin analogs with potentantibacterial and antitubercular activity
Publication TypeJournal Article
Year of Publication2018
AuthorsWagh, MA, Baravkar, SB, Jedhe, GS, Borkute, R, Choudhari, AS, Sarkar, D, Sanjayan, GJ
JournalChemistrySelect
Volume3
Issue11
Pagination3122-3126
Date PublishedMAR
Abstract

Ureidopenicillins are a class of penicillins which are antibiotics active against gram-negative bacteria. Herein, we report the synthesis of 2-aminothiophene-tethered ureidopenicillin analogues and their in vitro antibacterial and antitubercular activity. Intriguingly, unlike the reported ureidopenicillins which are active against gram-negative bacteria, the synthesised 2-aminothiophene-tethered ureidopenicillins were significantly active against Gram-positive bacterial strains and showed moderate inhibition towards gram-negative bacterial strains. Among all the analogs, compound 1b containing 2-aminothiophene moiety with minimum inhibitory concentration (MIC): 0.29, 0.32, > 10, > 10 mg/ml for Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa, respectively, showed better anti-bacterial profile as compared to cephalexin and equipotent to ampicillin and amoxicillin on gram-positive bacterial strains. All the derivatives were also screened for anti-TB activity against mycobacterium tuberculosis H37Ra. Among the series, cycloocta-thiophene-tethered cephalexin analog 3c displayed excellent antitubercular activity with MIC values 0.78 mg/ml. Low cytotoxicity and high selectivity index indicate the efficacy of 3c against mycobacterial infections. The results from present study offer a novel approach to modify the existing drug class of ureidopenicillins to yield antimicrobials with promising utility.

DOI10.1002/slct.201800027
Type of Journal (Indian or Foreign)

Foreign

Impact Factor (IF)

Not Available

Divison category: 
Organic Chemistry