Dynemicins, new antibiotics with the 1,5-diyn-3-ene and anthraquinone subunit. II. Antitumor activity of dynemicin a and its triacetyl derivative.

Abstract

DynemicinA showedextremely potent in vitro cytotoxicity against a variety of murine and human tumor cells. In the experimental animal tumor models implanted ip with P388, L1210leukemias and B16 melanoma cells, dynemicin A administered ip significantly prolonged life-span of tumor-bearing mice with the wide range of activity. This antibiotic administered iv wasalso active against iv implanted P388 and L1210 leukemias. In the macromolecule biosynthesis of B16 melanoma cells, dynemicin A inhibited DNAsynthesis specifically. The triacetyl derivative exhibited similar in vitro and in vivo antitumor activities to those of the parent antibiotic.

Enzymatic Activation of DNA Cleavage by Dynemicin A and Synthetic Analogs

“…Isolated from the fermentation broth of the microorganism Micromonospora chersina (Konishi et al, 1990(Konishi et al, , 1991, dynemicin A (1) is an exceedingly potent cytotoxin with LD 50 values in the picogram to nanogram per milliliter range against a variety of tumor cell lines (Kamei et al, 1991). Dynemicin A (1) is structurally unique among the naturally occurring antitumor agents, possessing features characteristic of both the anthracycline (Priebe, 1995) and enediyne antibiotics (Nicolaou & Dai, 1991).…”

Frankia colletiae sp. nov., a nitrogen-fixing actinobacterium isolated from Colletia cruciata

“…The genome sequences of strains Cc1.17 T and BMG5.12 T shared several BGCs that encode for: (i) bacillomycin D, isolated from Bacillus amyloliquefaciens , which was found to have antifungal activity against Fusarium graminearum [50]; (ii) naphthomycin A, extracted from Streptomyces collinus , which showed antimicrobial and antitumor activities [51]; (iii) mediomycin A, produced by Streptomyces mediocidicus ATCC23936, which has a broad spectrum of antifungal activity [52]; (iv) elaiophylin, which is a macrodiolide antibiotic isolated from Streptomyces hygroscopicus 17 997 [53]; (v) herboxidiene, which is produced by Streptomyces chromofuscus A7847 and exhibits antitumour activity [54]; (vi) tetronasin, which is an ionophore antibiotic isolated from Streptomyces longisporoflavus NCIB 11426 that showed antimicrobial activity mainly against ruminal Gram positive, protozoa and anaerobic fungus [55–57]; (vii) argimycin P (I, II, III IV, V, VI), which is a group of alkaloid compounds discovered in Stretpomyces argillaceus ATCC 12956 [58]; (viii) argimycin P III, known as nigrifactin and showed antihistaminic activity [59]; (ix) dynemicin, produced by Micromonospora chersina M956-1 and shows anticancer and antibiotic activities [60, 61]; and frankiamicin, which is a type II polyketide produced by Frankia sp. EAN1pec and shows antimicrobial activity against methicillin-resistant Staphylococcus aureus [62].…”

Anthraquinone-fused enediynes: discovery, biosynthesis and development

“…Shortly after the discovery of DYN A, Kamei and co-workers reported its antitumor activity. 53 Both DYN A and triacetyl DYN A exhibited high in vitro cytotoxicity against various murine and human cancer cell lines, such as B16-F10 (murine melanoma), HCT-116 (human colon carcinoma), P388 (murine leukemia), vincristine-resistant subline of P388 (P388/VCR) and doxorubicin-resistant subline (P388/ADM), as well as K562 (human myelogenous leukemia), with IC 50 values ranging from 0.0027 to 4 ng mL −1 . The in vivo experiment showed that DYN A administrated ip gave significant antitumor activity in mice with ip implanted P388 and L1210 leukemia and B16 melanoma.…”