A biological screening study of an actinomycetes strain assembly was conducted using a cell-based cytotoxicity assay. The CKK1019 strain was isolated from a sea sand sample. Cytotoxicity-guided fractionation of the CKK1019 strain culture broth, which exhibited cytotoxicity, led to the isolation of chromomycins A2 (1) and A3 (2). 1 and 2 showed potent cytotoxicity against the human gastric adenocarcinoma (AGS) cell line (IC50 1; 1.7 and 2; 22.1 nM), as well as strong inhibitory effects against TCF/β-catenin transcription (IC50 1; 1.8 and 2; 15.9 nM). 2 showed the ability to overcome tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) resistance. To the best of our knowledge, the effects of chromomycins A2 (1) and A3 (2) on TRAIL resistance-overcoming activity, and on the Wnt signaling pathway, have not been reported previously. Thus, 1 and 2 warrant potential drug lead studies in relation to TRAIL-resistant and Wnt signal-related diseases and offer potentially useful chemical probes for investigating TRAIL resistance and the Wnt signaling pathway.

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The antibiotic β-indomycinone was isolated from Streptomyces sp. IFM11607 by cytotoxicity-guided fractionation against human gastric adenocarcinoma AGS cells, and the geometry of its Δ 17,18-double bond was revised from E to Z based on the coupling constant.

In 2017, Leoni et al. reported myticalins as novel cationic linear antimicrobial peptides obtained from marine mussels. The authors focused on myticalin A6 (29 amino acids), which has a relatively short chain length among myticalins and contains a repeating X-proline(Pro)-arginine (Arg) sequence in its structure. We investigated the antimicrobial activity of myticalin A6 against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus (S. aureus). Fragment derivatives of myticalin A6 were synthesized, and the site required for expression of antimicrobial activity was examined. To investigate the structure-antimicrobial activity relationship of myticalin A6, short-chain derivatives and partially substituted derivatives were synthesized, and the antimicrobial activity was measured. Furthermore, some cyclized derivatives were synthesized and examined for antimicrobial activity. Circular dichroism (CD) spectroscopy of myticalin A6 and its derivatives was carried out to evaluate the secondary structure. Myticalin A6 exhibited an antimicrobial activity of 1.9 µM against S. aureus. Myticalin A6 (3-23)-OH (21 amino acids) exhibited an antimicrobial activity of 2.4 µM against S. aureus, suggesting that the X-Pro-Arg repeat sequence is important for antimicrobial activity. Derivatives with different CD measurement results from myticalin A6 (3-23)-OH exhibited decreased activity. The myticalin A6 (3-23)-OH derivative in which all Arg residues were replaced with lysine (Lys) residues exhibited reduced antimicrobial activity against S. aureus. We succeeded in synthesizing cyclic derivatives using 9-fluorenylmethoxycarbonyl (Fmoc)-aspartic acid (Asp)(Wang resin)-[2-phenylisopropyl ester (OPis)], but the yield of derivatives with 21 amino acids was decreased. The myticalin derivatives synthesized in this study did not exhibit any enhancement in antimicrobial activity due to cyclization.