In vitro metabolism of furazolidone by milk xanthine oxidase and rat liver homogenate yielded approximately equal amounts (30%) of 2,3-dihydro-3-cyano-methyl-2-hydroxyl-5-nitro-1a,2-di(2-oxo-oxazolidine-3-yl)imi nomethylfuro(2,3b)furan, and 3-(4-cyano-2-oxobutyl-lideneamino)-2-oxazolidone. The latter was also isolated from the urine of rabbits given on oral dose of furazolidone.
Furazolidone is an antimicrobial compound used in human and veterinary medicine. The aim of this investigation was to determine its genotoxic capacity in vitro and in vivo. We used the human lymphocyte culture system to detect the effect of 2.0, 4.0, 6.0, 8.0, or 10.0 ug/ml, and the mouse bone marrow assay to determine the effect of 8.6, 30.0, or 75.0 mg/kg furazolidone. In both systems we determined the frequency of sister-chromatid exchanges (SCE), the cell proliferation kinetics (CPK), and the mitotic index (MI). The in vitro results showed a significant SCE increase starting from the second dose tested and a CPK and MI decrease starting from the third dose. The in vivo results showed a SCE increase with the two high doses tested, but no significant modification was found in the CPK and MI with the three doses tested in the experiment.
In vitro metabolism of furazolidone (N-(5-nitro-2-furfuryliden)-3-amino-2-oxazolidone) was investigated by using milk xanthine oxidase and rat liver 9000 g supernatant. A new type of reduction product was isolated as 1 of the main metabolites from the incubation mixture and it was tentatively identified as 2,3-dihydro-3-cyanomethyl-2-hydroxyl-5-nitro-1a,2-di(2-oxo-oxazolidin-3-yl)imino methyl-furo(2,3-b)furan. The formation of N-(5-amino-2-furfurylidene)-3-amino-2-oxazolidone as a minor metabolite of nitrofuran in a milk xanthine oxidase system was demonstrated. The aminofuran derivative was easily degraded by milk xanthine oxidase under aerobic, but not anaerobic, conditions. The degradation appears to be due to superoxide anion radicals, hydroxy radicals and/or singlet O2, which are produced in this enzyme system. (Furazolidone, an antibacterial nitrofuran widely used as a veterinary medicine, was mutagenic in Escherichia coli WP2 and Salmonella typhimurium TA100 and tumorigenic in rats).
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
没有关于人类的数据。动物致癌性证据不足。总体评估：第3组：该物质对人类致癌性无法分类。
No data are available in humans. Inadequate evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent is not classifiable as to its carcinogenicity to humans.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
国际癌症研究机构致癌物：呋喃唑酮
IARC Carcinogenic Agent:Furazolidone
来源:International Agency for Research on Cancer (IARC)
毒理性
致癌物分类
国际癌症研究机构（IARC）致癌物分类：第3组：对其对人类的致癌性无法分类
IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans
来源:International Agency for Research on Cancer (IARC)
毒理性
致癌物分类
国际癌症研究机构专论：第31卷（1983年）一些食品添加剂、饲料添加剂和天然存在物质
IARC Monographs:Volume 31: (1983) Some Food Additives, Feed Additives and Naturally Occurring Substances
来源:International Agency for Research on Cancer (IARC)
毒理性
副作用
皮肤致敏剂 - 一种可以诱导皮肤产生过敏反应的制剂。
Skin Sensitizer - An agent that can induce an allergic reaction in the skin.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
吸收、分配和排泄
在大鼠单次口服剂量为100毫克/千克体重后，只有3%的剂量以未代谢化合物的形式在粪便中回收。
After a single oral dose of 100 mg/kg body weight to rats, only 3% of the dose was recovered in the feces as unmetabolized compound.
[EN] DERIVATIVES OF AMANITA TOXINS AND THEIR CONJUGATION TO A CELL BINDING MOLECULE<br/>[FR] DÉRIVÉS DE TOXINES D'AMANITES ET LEUR CONJUGAISON À UNE MOLÉCULE DE LIAISON CELLULAIRE
申请人：HANGZHOU DAC BIOTECH CO LTD
公开号：WO2017046658A1
公开（公告）日：2017-03-23
Derivatives of Amernita toxins of Formula (I), wherein, formula (a) R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R 10, X, L, m, n and Q are defined herein. The preparation of the derivatives. The therapeutic use of the derivatives in the targeted treatment of cancers, autoimmune disorders, and infectious diseases.
[EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
申请人：HANGZHOU DAC BIOTECH CO LTD
公开号：WO2020257998A1
公开（公告）日：2020-12-30
Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.
[EN] CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES<br/>[FR] DÉRIVÉ DE DIMÈRE DE PYRROLOBENZODIAZÉPINE RÉTICULÉ (PBD) ET SES CONJUGUÉS
申请人：HANGZHOU DAC BIOTECH CO LTD
公开号：WO2020006722A1
公开（公告）日：2020-01-09
A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.
The present invention relates to substituted tricyclic triazole compounds and compositions comprising substituted tricyclic triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a compound of the invention, or a composition comprising such a compound.
[EN] COMPOSITIONS AND METHODS FOR THE TREATMENT OF BACTERIAL INFECTIONS<br/>[FR] COMPOSÉS ET MÉTHODES POUR LE TRAITEMENT D'INFECTIONS BACTÉRIENNES
申请人：CIDARA THERAPEUTICS INC
公开号：WO2018006063A1
公开（公告）日：2018-01-04
Compositions and methods for the treatment of bacterial infections include compounds containing dimers of cyclic heptapeptides conjugated to one or more monosaccharide or oligosaccharide moieties. In particular, compounds can be used in the treatment of bacterial infections caused by Gram-negative bacteria.
