Inhibitory Effects of Nitrogenous Metabolites from a Marine-Derived Streptomyces bacillaris on Isocitrate Lyase of Candida albicans

Abstract

Two nitrogenous metabolites, bacillimide (1) and bacillapyrrole (2), were isolated from the culture broth of the marine-derived actinomycete Streptomyces bacillaris. Based on the results of combined spectroscopic and chemical analyses, the structure of bacillimide (1) was determined to be a new cyclopenta[c]pyrrole-1,3-dione bearing a methylsulfide group, while the previously reported bacillapyrrole (2) was fully characterized for the first time as a pyrrole-carboxamide bearing an alkyl sulfoxide side chain. Bacillimide (1) and bacillapyrrole (2) exerted moderate (IC50 = 44.24 μM) and weak (IC50 = 190.45 μM) inhibitory effects on Candida albicans isocitrate lyase, respectively. Based on the growth phenotype using icl-deletion mutants and icl expression analyses, we determined that bacillimide (1) inhibits the transcriptional level of icl in C. albicans under C2-carbon-utilizing conditions.

Integrated Bioinformatics-Based Subtractive Genomics Approach to Decipher the Therapeutic Drug Target and Its Possible Intervention against Brucellosis

“…ICL has been classified as a promiscuous target for M. tuberculosis due to its persistence and constitutes a target for antituberculotic agents [ 31 ]. Similarly, Chung et al also target the ICL protein for Candida albicans [ 79 ]. ICL has recently been widely targeted for the cure of numerous bacterial infections and thus can also be used as a potential target for B. suis 1330.…”

Marine natural products

“…A methylsulfide substituted cyclopenta[ c ]pyrrole-1,3-dione bacillimide 153 and a pyrrole-carboxamide containing bacillapyrrole 154 were reported from a sediment-derived S. bacillaris . 46 Other Streptomyces -sourced alkaloids included the strepotindoles A – D 155 – 158 , 47 streptocarbazoles F–H 159 – 161 , 48 penzonemycins A 162 and B 163 and demethylmycemycin A 164 , 49 as well as an indole, streptoprenylindole D 165 , co-isolated with a diterpene, 15-hydroxycyclooctatin 166 . 50 Piercidins A5 167 and G1 168 were isolated from a sediment-derived Streptomyces sp.…”

Marine Streptomyces-Derived Novel Alkaloids Discovered in the Past Decade

“…Three thio-containing pyrrolone-based alkaloids (60-62, Figure 7) were discovered from two marine Streptomyces [46,47]. Thiolopyrrolone A (60) had an unusual macrocyclic skeleton and also inhibited Bacille Calmette-Guérin (BCG), M. tuberculosis, and S. aureus, with MIC values of 10, 10 and 100 µg/mL, respectively.…”

“…Compound 70 had antiproliferative effects against MDA-MB-231 cells and A549 cells at 10 µM, with growth inhibition rates of 10.2% and 7.3%. An unusual PBD derivative, 7-methoxy-8-hydroxy cycloanthranilylproline (71), along with a known analogue (72), was isolated from marine S. cacaoi 14CM034 and displayed antimicrobial effects on E. coli, MRSA, E. faecium, P. aeruginosa and C. albicans, with MIC values ranging from Three thio-containing pyrrolone-based alkaloids (60-62, Figure 7) were discovered from two marine Streptomyces [46,47]. Thiolopyrrolone A (60) had an unusual macrocyclic skeleton and also inhibited Bacille Calmette-Guérin (BCG), M. tuberculosis, and S. aureus, with MIC values of 10, 10 and 100 µg/mL, respectively.…”