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This study reports the isolation and characterization of a Streptomyces sp. from soil, capable of producing bioactive secondary metabolites active against a variety of bacterial human pathogens. We targeted the antimicrobial activity against Escherichia coli ATCC-BAA 2469, a clinically relevant strain of bacteria harbouring resistance genes for carbapenems, extended spectrum beta-lactams, tetracyclines, fluoroquinones, etc. Preliminary screening using the spot inoculation technique identified Streptomyces sp. NP73 as the potent strain among the 74 isolated Actinomycetia strain. 16S rRNA gene and whole genome sequencing (WGS) confirmed its taxonomical identity and helped in the construction of the phylogenetic tree. WGS revealed the predicted pathways and biosynthetic gene clusters responsible for producing various types of antibiotics including the isolated compound. Bioactivity guided fractionation and chemical characterization of the active fraction, carried out using liquid chromatography, gas chromatography-mass spectrometry, infra-red spectroscopy, and nuclear magnetic resonance spectroscopy, led to the tentative identification of the active compound as Pyrrolo[1,2-a] pyrazine-1,4-dione, hexahydro-, a diketopiperazine molecule. This compound exhibited excellent antimicrobial and anti-biofilm properties against E. coli ATCC-BAA 2469 with an MIC value of 15.64 µg ml−1, and the low cytotoxicity of the compound identified in this study provides hope for future drug development. [ABSTRACT FROM AUTHOR]

The activity of sodium glucose co-transporter 2 (SGLT2) has always been an important parameter influencing chronic kidney disease in type-2 diabetic patients. Herein, we have meticulously designed, synthesized, and evaluated several novel steroidal pyrimidine molecules that possess the capability to successfully bind to the SGLT2 protein and inhibit its activity, thereby remedying kidney-related ailments in diabetic patients. The lead steroidal pyrimidine compounds were selected after virtually screening from a library of probable N -heterocyclic steroidal scaffolds. A nano-catalyzed synthetic route was also explored for the synthesis of the steroidal pyrimidine analogs demonstrating an environmentally benign protocol. Extensive in vitro investigations encompassing SGLT2 screening assays and cell viability assessments were conducted on the synthesized compounds. Among the steroidal pyrimidine derivatives evaluated, compound 9a exhibited the highest SGLT2 inhibition activity and underwent further scrutiny. Western blot analysis was employed to determine the impact of 9a on inflammatory and fibrotic proteins, aiming to elucidate its mechanism of action. Additionally, in silico analyses were performed to illuminate the structural dynamics and molecular interaction mechanism of 9a. The overall investigation is crucial for advancing the development of the next generation of anti-diabetic drugs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)