Novel tetracycline SBR-22 is a functional moiety deviation and bioactive against multidrug resistant strains

摘要

A new tetracycline analogue SBR-22 was isolated using bioactivity guided screening of the Streptomyces psammoticus 125-vr, from sea residues of the Visakhapatnam coast of South India. Based on spectral data, the name and structure of the antibiotic SBR-22 were identified as 1,5-dihydroxy- 5-methyl- 7- (N,N-dimethyl) amino- 6,8,11,12- tetraoxo- 7,9,10 -hexahydro- naphthacene. Unlike the standard oxytetracycline pharmacophore (OTP) at C2 and C1 positions, the SBR-22 molecule lacked (C9) -carbamido and (C10) keto functional groups. Furthermore, the oxidation of the B-ring, caused by the presence of two keto carbonyls at opposite positions, resulted in a Quinone ring system, making it an effective antibiotic. Unlike the OTP molecule, four prime functional groups in the A and B-rings were either absent or altered in this native novel molecule SBR-22, which successfully retained its bioactivity against inhibit multidrug resistant strains of bacteria. Hence, this new analogue SBR-22 is effective (64 mu g/ml(-1) minimum inhibitory concentration (MIC90)) against methicillin resistant Gram-positive bacteria Staphylococcus aureus and human pathogenic fungi Aspergillus wentii and A. niger (42 mu g/ml(-1) of MIC90). Interestingly, it can also inhibit MDRS of Pseudomonas aeruginosa and yeast Candida albicans (MIC90 of 128 mu g/ml(-1)), respectively.