Topoisomerase I inhibitor 7 (Compound 8) 是有效的Topoisomerase I 抑制剂。Topoisomerase I inhibitor 7 显著抑制肿瘤生长(高达 79%)。在接受 P388 淋巴瘤移植的小鼠模型中,Topoisomerase I inhibitor 7延长了小鼠寿命(153%)。
Anguinomycin A is an antibiotic first isolated from a Streptomyces sp. and analog of leptomycin B that is highly cytotoxic to mouse P388 leukemia cells in vitro (IC50 = 0.1-0.2 ng/ml). It also demonstrates antitumor activity at 62.5 μg/kg/day against Lewis lung carcinoma in mice.
Thiocoraline is a depsipeptide and DNAbis-intercalator originally isolated fromMicromonosporawith antibacterial and anticancer activities.1,2It is active against the Gram-positive bacteriaS. aureus,B. subtilis, andM. luteus(MICs = 0.05, 0.05, and 0.03 μg ml, respectively) but not Gram-negativeE. coli,K. pneumoniae, orP. aeruginosa(MICs = >100 μg ml for all).1Thiocoraline inhibits RNA and DNA polymerase and thymidylate synthase (IC50s = 6, 6, and 15 μg ml, respectively), as well as RNA and DNA synthesisin vitro(IC50s = 0.008 and 0.4 μg ml, respectively). It is cytotoxic to P388, A549, HT-29, and MEL-28 cancer cells (IC50s = 0.002, 0.002, 0.01, and 0.002 μg ml, respectively). 1.Romero, F., Espilego, F., Pérez Baz, J., et al.Thiocoraline, a new depsipeptide with antitumor activity produced by a marine Micromonospora. I. Taxonomy, fermentation, isolation, and biological activitiesJ. Antibiot. (Tokyo)50(9)734-737(1997) 2.Negri, A., Marco, E., García-Hernández, V., et al.Antitumor activity, X-ray crystal structure, and DNA binding properties of thiocoraline A, a natural bisintercalating thiodepsipeptideJ. Med. Chem.50(14)3322-3333(2007)
19,20-Epoxycytochalasin D is a fungal metabolite that has been found in the endophytic fungus Nemania sp. UM10M. It is active against the chloroquine-sensitive and -resistant strains of P. falciparum (MIC = 0.4 ng ml for both) without inducing cytotoxicity in Vero cells. It is cytotoxic to BT-549, LLC-PK11, and P388 cells (IC50s = 7.84, 8.4, and 0.16 µM, respectively) but not SK-MEL, KB, or SKOV3 cells up to a concentration of 10 µM.
(E)-5-(2-Bromovinyl)uracil (BVU) is a pyrimidine base and an inactive metabolite of the antiviral agents sorivudine and (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) that may be regenerated to BVDU in vivo. BVU irreversibly inactivates dihydropyrimidine dehydrogenase (DPD) in an NADPH-dependent manner. It enhances the efficacy of the chemotherapeutic agent and DPD substrate 5-fluorouracil in a P388 murine leukemia model when administered at a dose of 200 μmol kg, increasing survival time.
Saquayamycin B is a glycoside of aquayamycin that acts on Gram-positive bacteria and inhibits the growth of adriamycin-sensitive and adriamycin-resistant P388 leukemia cells.
(+)-Goniothalesdiol, isolated from the bark of the Malaysian tree G. borneensis, is a tetrahydrofuran compound known to have significant cytotoxic effects against P388 mouse leukemia cells and pesticidal activities. It has been shown to have promising cytotoxic activity against p388 mouse leukemia cells (ED50 ≥30 μg ml).
Pericosine A is a fungal metabolite that has been found inP. byssoidesand has anticancer activity.1It inhibits the growth of a variety of cancer cells, including breast, colon, lung, ovary, stomach, and prostate cell lines (GI50s = 0.05-24.55 μM) and increases survival in a P388 mouse xenograft model when administered at a dose of 25 mg/kg. Pericosine A inhibits EGFR by 40 to 70% when used at a concentration of 100 μg/ml. It also reacts with organosulfur compounds in skunk spray to form stable thioethers as odorless products.2 1.Yamada, T., Iritani, M., Ohishi, H., et al.Pericosines, antitumour metabolites from the sea hare-derived fungus Periconia byssoides. Structures and biological activitiesOrg. Biomol. Chem.5(24)3979-3986(2007) 2.Du, L., Munteanu, C., King, J.B., et al.An electrophilic natural product provides a safe and robust odor neutralization approach to counteract malodorous organosulfur metabolites encountered in skunk sprayJ. Nat. Prod.82(7)1989-1999(2019)