1. Induction of mitochondria-mediated apoptosis and suppression of tumor growth in zebrafish xenograft model by cyclic dipeptides identified from Exiguobacterium acetylicum
Hans-Uwe Dahms,Charles Chien-Chih Chiu,Sekar Jinendiran,Vinoth Kumar Ponnusamy,B S Dileep Kumar,Weilin Teng,Wangta Liu,Natesan Sivakumar Sci Rep . 2020 Aug 13;10(1):13721. doi: 10.1038/s41598-020-70516-x.
Colorectal cancer is the most common type of gastrointestinal cancers with poor survival and limited therapeutic options. In this study, four structurally different cyclic dipeptides (or diketopiperazine) were isolated and identified as cyclo (L-Pro-L-Leu), cyclo (L-Pro-L-Val), cyclo (L-Pro-L-Phe) and cyclo (L-Pro-L-Tyr) from the ethyl acetate extract in the cell-free filtrate of Exiguobacterium acetylicum S01. The anticancer potential of identified DKPs on colorectal cancer HT-29 cells in vitro and in vivo zebrafish xenograft model was evaluated. The MTT (3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide)) assay showed that four DKPs exhibited significant inhibition of HT-29 cells viability in a dose-dependent manner whereas there were no cytotoxic effects on normal mouse fibroblast 3T3 cells. Also, we observed that all DKPs induce early and late apoptotic cell death in HT-29 cells. Moreover, the expression levels of apoptotic (cytochrome-c, caspase-3 and Bid) and anti-apoptotic (Bcl-2) markers were up- and down-regulated in HT-29 cells in response to DKPs treatments. Furthermore, these four DKPs remarkably inhibited the tumor progression in a zebrafish xenograft model within a nonlethal dose range. Overall, our findings suggest that cyclic dipeptides derived from E. acetylicum S01 could be promising chemopreventive/ therapeutic candidates against cancer.
2. Isolation and Structure Identification of Novel Brominated Diketopiperazines from Nocardia ignorata-A Lichen-Associated Actinobacterium
Nicolas Gouault,Sophie Tomasi,Alba Noël,Jean-Pierre Hurvois,Isabelle Rouaud,Solenn Ferron Molecules . 2017 Feb 28;22(3):371. doi: 10.3390/molecules22030371.
Actinobacteria are well known for their potential in biotechnology and their production of metabolites of interest. Lichens are a promising source of new bacterial strains, especially Actinobacteria, which afford a broad chemical diversity. In this context, the culture medium of the actinobacteriumNocardia ignorata,isolated from the terrestrial lichenCollema auriforme, was studied. The strain was cultivated in a BioFlo 115 bioreactor, and the culture medium was extracted using an XAD7HP resin. Five known diketopiperazines: cyclo (l-Pro-l-OMet) (1), cyclo (l-Pro-l-Tyr) (2), cyclo (d-Pro-l-Tyr) (3), cyclo (l-Pro-l-Val) (4), cyclo (l-Pro-l-Leu) (5), and one auxin derivative: indole-carboxaldehyde (8) were isolated, along with two new brominated diketopiperazines: cyclo (d-Pro-l-Br-Tyr) (6) and cyclo (l-Pro-l-Br-Tyr) (7). Structure elucidation was performed using HRMS and 1D and 2D NMR analysis, and the synthesis of compounds6and7was carried out in order to confirm their structure.
3. Diversity and Antimicrobial Activity of Vietnamese Sponge-Associated Bacteria
Hauke Smidt,Nguyen Thi Kim Cuc,Pham Viet Cuong,Detmer Sipkema,Ton That Huu Dat Mar Drugs . 2021 Jun 22;19(7):353. doi: 10.3390/md19070353.
This study aimed to assess the diversity and antimicrobial activity of cultivable bacteria associated with Vietnamese sponges. In total, 460 bacterial isolates were obtained from 18 marine sponges. Of these, 58.3% belonged toProteobacteria, 16.5% toActinobacteria, 18.0% toFirmicutes, and 7.2% toBacteroidetes. At the genus level, isolated strains belonged to 55 genera, of which several genera, such asBacillus,Pseudovibrio,Ruegeria,Vibrio, andStreptomyces, were the most predominant. Culture media influenced the cultivable bacterial composition, whereas, from different sponge species, similar cultivable bacteria were recovered. Interestingly, there was little overlap of bacterial composition associated with sponges when the taxa isolated were compared to cultivation-independent data. Subsequent antimicrobial assays showed that 90 isolated strains exhibited antimicrobial activity against at least one of seven indicator microorganisms. From the culture broth of the isolated strain with the strongest activity (Bacillussp. M1_CRV_171), four secondary metabolites were isolated and identified, including cyclo(L-Pro-L-Tyr) (1), macrolactin A (2), macrolactin H (3), and 15,17-epoxy-16-hydroxy macrolactin A (4). Of these, compounds2-4exhibited antimicrobial activity against a broad spectrum of reference microorganisms.
4. New cytotoxic furan from the marine sediment-derived fungi Aspergillus niger
Maria da Conceição F de Oliveira,Raimundo Braz-Filho,Lucas M Abreu,Mary Anne S Lima,Natália N Saraiva,Diego V Wilke,Katharine G D Florêncio,Antonia T A Pimenta,Barbara S F Rodrigues,Ludwig H Pfenning,Paula Karina S Uchoa Nat Prod Res . 2017 Nov;31(22):2599-2603. doi: 10.1080/14786419.2017.1283499.
A fungal strain of Aspergillus niger was recovered from sediments collected in the Northeast coast of Brazil (Pecém's offshore port terminal). Cultivation in different growth media yielded a new ester furan derivative, 1, along with malformin A1, malformin C, cyclo (trans-4-hydroxy-L-Pro-L-Leu), cyclo (trans-4-hydroxy-L-Pro-L-Phe), cyclo (L-Pro-L-Leu), cyclo (L-Pro-L-Phe), pseurotin D, pseurotin A, chlovalicin, cyclo (L-Pro-L-Tyr) and cyclo (L-Pro-L-Val). Compound 1 was cytotoxic against HCT-116 cell line, showing IC50= 2.9 μg/mL (CI 95% from 1.8 to 4.7 μg/mL).
