https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

https://chemistry.mdma.ch/hiveboard/rhodium/pdf/archive/merbst/quinoline1999.pdf

Quinoline, quinazoline and acridone alkaloids

The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras

Inhibitors of farnesyl protein transferase

https://backend.orbit.dtu.dk/ws/files/101356374/elsevier_8_.pdf

Phylogeny, identification and nomenclature of the genus Aspergillus

Inhibitors of the breast cancer resistance protein (BCRP/ABCG2) multidrug transporter are of interest as chemosensitizers for clinical drug resistance, for improving the pharmacokinetics of substrate chemotherapeutic drugs, and in functional assays of BCRP activity for tailoring chemotherapy. The fungal toxin fumitremorgin C (FTC) is a potent and specific inhibitor of BCRP, but its neurotoxic effects preclude use in vivo. We have therefore evaluated a new tetracyclic analogue of FTC, Ko143, as a practical inhibitor of BCRP, comparing it with two other analogues in the same class and with GF120918. All three FTC analogues are effective inhibitors of both mouse Bcrp1 and human BCRP, proving highly active for increasing the intracellular drug accumulation and reversing Bcrp1/BCRP-mediated multidrug resistance. Indeed, Ko143 appears to be the most potent BCRP inhibitor known thus far. In contrast, the compounds have only low activity against P-glycoprotein, the multidrug resistance-associated protein (MRP1), or other known drug transporters. They are nontoxic in vitro at useful concentrations and evinced no signs of toxicity in mice at high oral or i.p. doses. Administered p.o. to inhibit intestinal Bcrp1, Ko143 markedly increased the oral availability of topotecan in mice. It is thus the first highly potent and specific BCRP inhibitor applicable in vivo. As such, Ko143 and other FTC analogues of this type represent valuable reagents for analysis of drug resistance mechanisms and may be candidates for development as clinical BCRP inhibitors.

https://mct.aacrjournals.org/content/molcanther/1/6/417.full.pdf

Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C.

According to the traditional usage of the plant for antiinflammation and analgesia, Leucas aspera was tested for its prostaglandin (PG) inhibitory and antioxidant activities. The extract showed both activities, i.e., inhibition at 3 x 10(-4) g/ml against PGE(1)- and PGE(2)-induced contractions in guinea pig ileum and a 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect. The separation guided by the activities in these dual assay methods provided eight lignans and four flavonoids, LA-1- -12, among which LA-1- -7 and LA-10- -12 were identified as nectandrin B, meso-dihydroguaiaretic acid, macelignan, acacetin, apigenin 7-O-[6"-O-(p-coumaroyl)-beta-D-glucoside], chrysoeriol, apigenin, erythro-2-(4-allyl-2, 6-dimethoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)propan-1-ol, myristargenol B, and machilin C, respectively. LA-8 was determined to be (-)-chicanine, the new antipode of the (+) compound, by spectroscopic methods including CD and ORD. Chiral-HPLC analysis of LA-9 showed that it was a mixture of two enantiomers, (7R, 8R)- and (7S, 8S)-licarin A. All of these components were first isolated from L. aspera. PG inhibition was observed in LA-1, LA-2, and LA-5, and antioxidant activity in LA-1- -3 and LA-8- -12.

Separation of Leucas aspera, a medicinal plant of Bangladesh, guided by prostaglandin inhibitory and antioxidant activities.

A mixed microbial culture capable of metabolizing deoxynivalenol was obtained from soil samples by an enrichment culture procedure. A bacterium (strain E3-39) isolated from the enrichment culture completely removed exogenously supplied deoxynivalenol from culture medium after incubation for 1 day. On the basis of morphological, physiological, and phylogenetic studies, strain E3-39 was classified as a bacterium belonging to the Agrobacterium-Rhizobium group. Thin-layer chromatographic analysis indicated the presence of one major and two minor metabolites of deoxynivalenol in ethyl acetate extracts of the E3-39 culture filtrates. The main metabolite was identified as 3-keto-4-deoxynivalenol by mass spectroscopy and 1H and 13C nuclear magnetic resonance analysis. The immunosuppressive toxicity of 3-keto-4-deoxynivalenol was evaluated by means of a bioassay based on the mitogen-induced and mitogen-free proliferations of mouse spleen lymphocytes. This compound exhibited a remarkably decreased (to less than one tenth) immunosuppressive toxicity relative to deoxynivalenol, indicating that the 3-OH group in deoxynivalenol is likely to be involved in exerting its immunosuppressive toxicity. Strain E3-39 was also capable of transforming 3-acetyldeoxynivalenol but not nivalenol and fusarenon-X.

Novel detoxification of the trichothecene mycotoxin deoxynivalenol by a soil bacterium isolated by enrichment culture.

By activity-oriented separation using the writhing method in mice, the analgesic components of Saposhnikovia root (Saposhnikovia divaricata Schischkin; Umbelliferae) were identified to be chromones, coumarins, polyacetylenes and 1-acylglycerols. Two new components, divaricatol and (3'S)-hydroxydeltoin, were also isolated. The most potent analgesia was observed in chromones such as divaricatol, ledebouriellol and hamaudol, which inhibited writhing inhibition at an oral dose of 1 mg/kg in mice. Acylglycerols also showed inhibition significantly at a dose of 5 mg/kg. In some pharmacological tests using sec-O-glucosylhamaudol, the compound showed analgesia by the tail pressure and the Randall & Selitto methods, and its writhing inhibition was not reversed by naloxone.

/pdf/analgesic-components-of-saposhnikovia-root-saposhnikovia-hcfohrq715.pdf

Analgesic components of saposhnikovia root (Saposhnikovia divaricata).

Fractionation guided by the immunosuppressive activity of the defatted AcOEt extract of an Ascomycete, Microascus tardifaciens, afforded eight constituents, questin (emodin 8-O-methylether) (1), rubrocristin (2), 5, 7-dihydroxy-4-methylphthalide (3), cladosporin (asperentin) (4), cladosporin 8-O-methylether (5), tardioxopiperazine A [cyclo-L-alanyl-5-isopentenyl-2-(1', 1'-dimethylallyl)-L-tryptophan] (6), tardioxopiperazine B [cyclo-L-alanyl-7-isopentenyl-2-(1', 1'-dimethylallyl)-L-tryptophan] (7), and asperflavin (8), among which 6 and 7 were new compounds. Compounds 1 and 2 showed considerably high immunosuppressive activity, 6 was moderate and, 3, 4, 5, 7 and 8 showed low activity.

https://cpb.pharm.or.jp/cpb/199910/C10_1426.PDF

Immunomodulatory constituents from an ascomycete, Microascus tardifaciens.

A new meroterpenoid named setosusin and two new tryptoquivalines were isolated as tremorgenic principles from an Ascomycete, Corynascus setosus, together with four known metabolited, fiscalin B, helvolic acid, helvolinic acid, and 2-(1-oxo-2-hydroxyethyl)furan. The structure of setosusin was determined from the chemical and spectral data and by X-ray crystallographic analysis of its deacetyl-dehydrated derivative. The two new tryptoquivalines were deduced to be 27-epi-isomers of tryptoquivaline and nortryptoquivaline from their spectral data supported by X-ray analysis.

Haruhiro Fujimoto

Papers

Separation of Leucas aspera, a medicinal plant of Bangladesh, guided by prostaglandin inhibitory and antioxidant activities.

Novel detoxification of the trichothecene mycotoxin deoxynivalenol by a soil bacterium isolated by enrichment culture.

Analgesic components of saposhnikovia root (Saposhnikovia divaricata).

Immunomodulatory constituents from an ascomycete, Microascus tardifaciens.

Isolation of New Tremorgenic Metabolites from an Ascomycete, Corynascus setosus.