Kumar, Nag S.’s team published research in Bioorganic & Medicinal Chemistry in 22 | CAS: 69626-75-1

Bioorganic & Medicinal Chemistry published new progress about 69626-75-1. 69626-75-1 belongs to benzofurans, auxiliary class Iodide,Benzofuran, name is 2-Iodobenzofuran, and the molecular formula is C8H5IO, SDS of cas: 69626-75-1.

Kumar, Nag S. published the artcileDiscovery and optimization of a new class of pyruvate kinase inhibitors as potential therapeutics for the treatment of methicillin-resistant Staphylococcus aureus infections, SDS of cas: 69626-75-1, the publication is Bioorganic & Medicinal Chemistry (2014), 22(5), 1708-1725, database is CAplus and MEDLINE.

A novel series of bis-indoles derived from naturally occurring marine alkaloid cis-3,4-dihydrohamacanthin B (I) was synthesized and evaluated as inhibitors of methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase (PK). PK is not only critical for bacterial survival which would make it a target for development of novel antibiotics, but it is reported to be one of the most highly connected ‘hub proteins’ in MRSA, and thus should be very sensitive to mutations and making it difficult for the bacteria to develop resistance. From the co-crystal structure of I bound to S. aureus PK we were able to identify the pharmacophore needed for activity. Consequently, we prepared simple direct linked bis-indoles such as 6,6′-dibromo-2,2′-biindolyl [II; R, R’ = 6,6′-dibromo (b)] that have similar anti-MRSA activity as compound I. Structure-activity relationship (SAR) studies on II led us to discover more potent compounds such as II [R, R’ = 6,5′-dibromo; 6-bromo-5′-chloro; 5,6,6′-tribromo; 5,6,5′-tribromo (c, d, k, m, resp.)] with enzyme inhibiting activities in the low nanomolar range that effectively inhibited the bacteria growth in culture with min. inhibitory concentrations (MIC) for MRSA as low as 0.5 μg/mL. Some potent PK inhibitors, such as IIb, exhibited attenuated antibacterial activity and were found to be substrates for an efflux mechanism in S. aureus. Studies comparing a wild type S. aureus with a construct (S. aureus LAC Δpyk::ErmR) that lacks PK activity confirmed that bactericidal activity of IId was PK-dependant.

Bioorganic & Medicinal Chemistry published new progress about 69626-75-1. 69626-75-1 belongs to benzofurans, auxiliary class Iodide,Benzofuran, name is 2-Iodobenzofuran, and the molecular formula is C8H5IO, SDS of cas: 69626-75-1.

Referemce:
https://en.wikipedia.org/wiki/Benzofuran,
Benzofuran | C8H6O – PubChem