Design and synthesis of 2-amino-thiophene-tethered ureidopenicillin analogs with potentantibacterial and antitubercular activity
| Title | Design and synthesis of 2-amino-thiophene-tethered ureidopenicillin analogs with potentantibacterial and antitubercular activity |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Wagh, MA, Baravkar, SB, Jedhe, GS, Borkute, R, Choudhari, AS, Sarkar, D, Sanjayan, GJ |
| Journal | ChemistrySelect |
| Volume | 3 |
| Issue | 11 |
| Pagination | 3122-3126 |
| Date Published | MAR |
| 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. |
| DOI | 10.1002/slct.201800027 |
| Type of Journal (Indian or Foreign) | Foreign |
| Impact Factor (IF) | Not Available |
Divison category:
Organic Chemistry