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1.
《Bioorganic & medicinal chemistry》2016,24(18):4023-4031
We report design, synthesis, and mechanistic studies of a new mitomycin tetramer 9 along with a new mitomycin dimer 10. Mitomycin 9 is a tetramer connected by the disulfide linker 11, and easily undergoes disulfide cleavage to provide two dimeric structures 9r that each contains a single thiol probe for activations. So, tetramer 9 as a precursor of 9r was specifically targeted to undergo double activations with a single probe. A tetramer 9 was synthesized using 1 and key intermediate 11, and a dimer 10 was synthesized from 1 and diamine 12. Activation studies revealed that 9 underwent effective double activations with a single probe by nucleophiles while the reference 10 did not. Evaluations of DNA ISC formations showed that 9 generated substantial levels of DNA ISC by nucleophilic activation while the references 10 and 2 did not. The effectiveness of 9 in activation and formation of DNA ISC per probe was verified by comparing with dimers 5–8 of double activations with two probes. These findings highlighted the role of a single thiol in 9r and demonstrated the intended double activations with a single probe, which marks the first case in mitomycin studies. 相似文献
2.
Chemical study of Piper crocatum leaves has led to isolation of a new megastigmane glucoside isomer (18), along with 23 known compounds including fifteen phenolic compounds (1–15), two monoterpenes (16 and 17), three sesquiterpenes (19–21), a phenolic amide glycoside (22), a neolignan (23), and a flavonoid C-glycoside (24). Structures of these compounds were identified via spectroscopic methods and compared with those reported in the literature. Seven compounds (7, 11, 13, 14, 17, 20, and 24) from the P. crocatum species and 17 others (1–6, 8–10, 12, 15–16, 18–19, and 21–23) from the Piper genus and Piperaceae family were isolated and reported for the first time. Furthermore, this study discusses chemotaxonomic relations between P. crocatum and other Piper species. 相似文献
3.
Jaekwang Lee Suyeal Bae Seo-hee Lee Hojin Choi Young Hoon Kim Soo Jin Kim Gyu Tae Park Seung Kee Moon Dal-Hyun Kim Sungsook Lee Soon Kil Ahn Nam Song Choi Kyung Joo Lee 《Bioorganic & medicinal chemistry letters》2010,20(21):6327-6330
Prodrugs have proven to be very useful in enhancing aqueous solubility of sparingly water-soluble drugs, thereby increasing in vivo efficacy without a need of special excipients. In vitro and in vivo evaluations of a number of amino acid prodrugs of 1, a previously identified potent tubulin polymerization inhibitor and cytotoxic against various cancer cell lines led to the discovery of 3·HCl (l-valine attached) which is highly efficacious in mouse xenografts bearing human cancer. Pharmacokinetic analysis in rats revealed that compound 1 was released immediately upon administration of 3·HCl intravenously, with rapid clearance of 3·HCl indicating the effective cleavage of prodrug. Compound 3·HCl (CKD-516) has now been progressed to phase 1 clinical trial. 相似文献
4.
Coumarins and other components of Daphne oleoides Schreb. subsp. oleoides from Majella National Park
The present study reports about the phytochemical analysis of a sample of Daphne oleoides Schreb. subsp. oleoides (family Thymelaeaceae) collected from the Majella National Park. Twenty components, belonging to different classes of natural products, have been identified by means of spectroscopic and spectrometric techniques: [monomeric (4), bis- (5, 7–10, 20) and trimeric coumarins (11), including aglycones and glycosides, coumarinolignoid (6); flavonoids (16–19); glycosidic furolignans (14, 15), glucosidic phenylpropanoids (12, 13), cyclic tetrapyrrole derivatives (2, 3), unsaturated triglyceride (1)]. Besides the chemosystematic markers of the genus (4–10, 12, 14–18, 20) several other components were identified for the first time in the species (17, 20) and/or in the Daphne genus (1–3, 13, 19). The observed composition was discussed from the chemotaxonomic standpoint and compared with those recognized from a Sardinian accession. It was observed a pronounced difference in the two metabolites patterns, most probably attributable to geographic isolation of the studied populations and, in some extent, also by the different environmental conditions, evidencing a possible tendency of D. oleoides to the infraspecific chemovariability. Considering the wide traditional uses of Daphne spp. in ethnomedicine of several countries, also the pharmacologic potential of the identified secondary metabolites is discussed. 相似文献
5.
Li Pan Young-Won Chin Hee-Byung Chai Tran Ngoc Ninh Djaja Djendoel Soejarto A. Douglas Kinghorn 《Bioorganic & medicinal chemistry》2009,17(6):2219-2224
Five new triterpenoids (1–5), together with two known quassinoids, bruceantin (6) and bruceine A (7), and a known flavonolignan, (?)-hydnocarpin (8), were isolated from the chloroform-soluble subfraction of a methanol extract of the combined twigs, leaves, and inflorescence of Brucea javanica collected in Vietnam. The structures of the new compounds 1–5 were established on the basis of spectroscopic methods. All isolates were evaluated for cytotoxicity against a small panel of human cancer cell lines. Quassinoids 6 and 7 were found to be highly active against these cell lines. (?)-Hydnocarpin (8) showed a potentiating effect when combined with both 6 and 7, during cytotoxicity testing using the MCF-7 human breast cancer cell line. 相似文献
6.
7.
Kyriaki Pegklidou Catherine Koukoulitsa Ioannis Nicolaou Vassilis J. Demopoulos 《Bioorganic & medicinal chemistry》2010,18(6):2107-2114
Pyrrolyl-propionic and butyric-acid derivatives 1 and 2 were synthesized in order to study the effect of the variation of the methylene chain in comparison to the previously reported pyrrolyl-acetic acid compound I, which was found as potent aldose reductase inhibitor, while the pyrrolyl-tetrazole derivatives 3–5 were prepared as a non-classical bioisosteres of a carboxylic acid moiety. Also, pyrrolyl-tetrazole isomers 6 and 7 without an alkyl chain between the two aromatic rings were synthesized. The in vitro aldose reductase inhibitory activity of the prepared 1–7 compounds were estimated and compared with that of the initial compound (I). Overall, the data indicate that the presented chemotypes 6 and 7 are a promising lead compounds for the development of selective aldose reductase inhibitors, aiming to the long-term complications of diabetes mellitus. 相似文献
8.
Tetsuyoshi Takamoto Hiroshi Omi Toshihiko Matsuzaki Rokuro Sudoh 《Carbohydrate research》1978,60(1):97-103
The nitromethane condensation-product (3) from 2,3-O-isopropylidene-D-ribose (2) underwent dehydration and subsequent thermal cyclization in dimethyl sulfoxide to give a mixture of α- and β-D-ribofuranosylnitromethane derivatives (5 and 6) in a ratio of 7:2. Heating of 6-O-benzoyl-1-deoxy-1-nitro-D-altritol (10) in water afforded α- and β-C-glycosyl derivatives (11 and 12) in a ratio of 2:3. Pure 11 and 12 gave the same mixture of 11 and 12 when heated in water, and similar epimerization of the isopropylidene acetals 5, 6, 13, and 14 proceeded readily upon heating, leading mainly to the thermodynamically more-stable α anomers. 相似文献
9.
Jun-Li Yang Trong Tuan Dao Tran Thi Hien Ya-Min Zhao Yan-Ping Shi 《Bioorganic & medicinal chemistry letters》2019,29(10):1162-1167
The rhizomes of Homalomena occulta are called Qian-nian-jian in Traditional Chinese Medicine (TCM), which is widely consumed in China owing to its health benefits for the treatment of rheumatoid arthritis and for strengthening tendons and bones. A phytochemical investigation on this famous TCM yielded 19 sesquiterpenoids (1–19) with various carbocyclic skeletons including isodaucane (2, 8, and 9), guaiane (3), eudesmane (4 and 10–15), oppositane (5, 16, and 17), and aromadendrane (18 and 19) types. The structures of new compounds, Homalomenins A-E (1–5), were determined by diverse spectroscopic data. Compound 1 possessed a rare sesquiterpenoid skeleton and compound 5 represented the first example of 1,4-oxa-oppositane sesquiterpenoid. These isolates were evaluated for their inhibitory effects on COX-2 mRNA, COX-2 protein expression, and prostaglandin E2 (PGE2) production in Raw264.7 cells, which demonstrated that compounds 5, 18, 19 showed potent anti-inflammatory activity by suppressing LPS-induced COX-2 expression and PGE2 production in a dose-dependent manner. 相似文献
10.
Chemical investigation of the traditional Chinese medicine Amomum kravanh led to the isolation of a new secolignan (1), two flavonoids (2 and 3), four monoterpenoids (4–7) and six steroids (8–13). Compounds 1, 5–8 and 12–13 were isolated from the family Zingiberaceae for the first time. Compound 1 is the first lignan reported in the genus Amomum and compound 8 is firstly described as a natural product, which could be of chemotaxonomic importance for the genus Amomum and family Zingiberaceae. 相似文献
11.
Predrag Novak Jill Barber Ana Čikoš Biljana Arsic Janez Plavec Gorjana Lazarevski Predrag Tepeš Nada Košutić-Hulita 《Bioorganic & medicinal chemistry》2009,17(16):5857-5867
The solution and solid state conformations of several 6-O-methyl homoerythromycins 1–4 were studied using a combination of X-ray crystallography, NMR spectroscopy and molecular modelling calculations. In the solid state 1 was found to exist as the two independent molecules with similar structures termed 3-endo-folded-out. In solution a significant conformational flexibility was noticed especially in the C2 to C5 region. The compounds 1 and 2 unlike 14-membered macrolides adopted the 3-endo-folded-out conformation while 3 and 4 existed in the classical folded-out conformation. TrNOESY and STD experiments showed that 1 and 2 bound to the Escherichia coli ribosome while 3 and 4, lacking the cladinose sugar, did not exhibit binding activities, this being in accordance with biochemical data. The bound conformations were found to be very similar to the free ones, some small differences were observed and discussed. The STD experiments provided evidence on binding epitopes. The structural parts of 1 and 2 in close contact with ribosome were similar, however the degree of saturation transfer was higher for 2. The differences between tr-NOE data and STD enhancements in 1 and 2 arouse as a consequence of structural changes upon binding and a closer proximity of 2 to the ribosome surface. An understanding of the molecular mechanisms involved in the interaction of macrolides with ribosomes can help in developing strategies aiming at design of potential inhibitors. 相似文献
12.
The monohydroxycarotenoids formed by diphenylamine-inhibited cultures of Rhodospirillum rubrum have been investigated. Nine have been isolated and identified as 1-hydroxy-1,2-dihydrophytofluene (1), 1-Hydroxy-1,2,7′,8′,11′,12′-hexahydrolycopene (2), chloroxanthin (3), 1-methoxy-1′-hydroxy-1,2,1′,2′-tetrahydrophytofluene (4a), 1′-hydroxy-3,4,1′,2′,11′,12′-hexahydrospheroidene (5, 1′-hydroxy-3,4,1′,2′-tetrahydrospheroidene (6, 1′-hydroxy 1′,2′-dihydrospheroidene (7), rhodovibrin (8a) and monodeme thylated spirilloxanthin (9). 4a, 5 and 6 are novel carotenoids, and a definite structure has been assigned to 2 for the first time; the structure of 1 has been amended. The possible role of these carotenoids in spirilloxanthin biosynthesis is discussed. 相似文献
13.
《Phytochemistry》2012
Abscisic acid (ABA, 1), a plant hormone, has electrophilicity derived almost entirely from the side-chain, 3-methylpenta-2,4-dienoic acid. The electrochemical property of ABA was investigated by analysis of its cathodic reaction. ABA methyl ester (1-Me) was reduced at a peak potential of −1.6 V to give a unique and unstable bicyclic compound (5-Me) as a major product at pH 3 and 7. This finding showed that an electron was absorbed in the conjugated dienecarboxyl group, and that C-5 with a high electron density attacked C-2′ through an intramolecular nucleophilic addition. At pH 10, in addition to 5-Me, a compound 4-Me was formed by isomerization of 5-Me under alkaline conditions. For a cathodic reaction of ABA at pH 3 and 7, compound 5 was a major product as well as in the case of ABA methyl ester. However, at pH 10, a dimer (6) with an epoxy group, 1′-deoxy-ABA (7) and other compounds were formed instead of compounds 4 and 5. Compounds 4 and 5 were biologically inactive, suggesting the importance of the electrophilic side-chain of ABA for biological activity. 相似文献
14.
epi-Androsterone 1 was converted into its hydrazone derivative through the reaction with hydrazine hydrate 80%. Hydrazonoandrostane derivative 2b reacted with hydrazonoyl halides in the presence of K2CO3 forming the corresponding hydrazopyridazinoandrostane derivatives 6a–d. The 3β-acetyl-17-hydrazonoandrostane derivative 2b reacted with a halogen reagent, benzoyl chloride, to form the non-cyclic 16-benzoylated hydrazone 9.On the other hand, compound 2b produced the corresponding pyridazinoandrostane derivatives 11 and 12 via its reaction with phenacyl bromide and chloroacetone respectively. Reaction of the hydrazono derivative 2b with benzaldehyde in the presence of acetic acid drops led to the formation of the benzylidenehydrazonoandrostane derivative 13. The product 14, phosphinom-ethylenehydrazonoandrostane was obtained by the reaction of the derivative 13 with trisdimethylaminophosphine in the presence of dry benzene. The reaction of compound 2b with phenyl isothiocyanate followed by boiling in chloroacetic acid or thioglycolic acid produced the pyrazoloandrostane derivatives 17 and 18 respectively. The biological activity of compounds 6a, 6d, 11, 12, and 15 was evaluated as inhibitor of growth in a human liver carcinoma cell line and doxorubicine was used for comparison. Compounds 15 and 12 showed a higher potency than the other tested compounds. 相似文献
15.
David Rennison Daniel Conole Malcolm D. Tingle Junpeng Yang Charles T. Eason Margaret A. Brimble 《Bioorganic & medicinal chemistry letters》2013,23(24):6629-6635
A number of structural analogues of the known toxicant para-aminopropiophenone (PAPP) have been prepared and evaluated for their capacity to induce methemoglobinemia—with a view to their possible application as humane pest control agents. It was found that an optimal lipophilicity for the formation of methemoglobin (metHb) in vitro existed for alkyl analogues of PAPP (aminophenones 1–20; compound 6 metHb% = 74.1 ± 2). Besides lipophilicity, this structural sub-class suggested there were certain structural requirements for activity, with both branched (10–16) and cyclic (17–20) alkyl analogues exhibiting inferior in vitro metHb induction. Of the four candidates (compounds 4, 6, 13 and 23) evaluated in vivo, 4 exhibited the greatest toxicity. In parallel, aminophenone bioisosteres, including oximes 30–32, sulfoxide 33, sulfone 34 and sulfonamides 35–36, were found to be inferior metHb inducers to lead ketone 4. Closer examination of Hammett substituent constants suggests that a particular combination of the field and resonance parameters may be significant with respect to the redox mechanisms behind PAPPs metHb toxicity. 相似文献
16.
Ryo C. Yanagita Hiroaki Kamachi Keisuke Tanaka Akira Murakami Yu Nakagawa Harukuni Tokuda Hiroshi Nagai Kazuhiro Irie 《Bioorganic & medicinal chemistry letters》2010,20(20):6064-6066
The 18-deoxy derivative (3) of a simplified analogue (1) of aplysiatoxin with antiproliferative activity was synthesized to examine the role of the phenolic hydroxyl group at position 18 in the biological activities of 1. Compound 3 as well as 1 showed significant affinity for protein kinase Cδ (PKCδ), and the antiproliferative activity of 3 was slightly higher than that of 1. However, the anti-tumor-promoting activity of 3 was less than that of 1 in vitro, suggesting that the phenolic hydroxyl group of 1 is necessary for the anti-tumor-promoting activity but not for the binding of PKCδ and antiproliferative activity. Moreover, PKC isozyme selectivity of 3 was similar to that of 1, suggesting non-PKC receptors for these compounds to play some roles in the anti-tumor-promoting activity of 1. 相似文献
17.
2-substitued-benzopyrimidinones 2 were synthesized in high to excellent yields in a single step via condensation of 2-aminobenzamide 1 with some aryl-aldehydes in the presence of iodine. Cyclocondensation reaction of hydrazides 3 which were obtained in two steps from benzopyrimidinones 2, with some electrophilic species such as 2,4-pentandione, 2,5-hexandione, 1-phenylbutan-1,3-dione and cyclic anyhdrides provided the new compounds 4a–c, 5a–c, 6a–c, 7a–c, 8a–c and 9a–c. The synthesized compounds were characterized by spectroscopic means. They were also evaluated for their anti-tyrosinase potential. The structure-activity relationship (SAR) was discussed on the basis of the molecular docking analysis. 相似文献
18.
Phytochemical investigation of the non-polar extract of Clusia burle-marxii led to the identification of a new steroid (1), along with friedelinol (2), β-sitosterol (3), friedelin (4), stigmast-5-en-3β,7β-diol (5), stigmast-5-en-3β,7α-diol (6), stigmasterol (7), sitostenone (8), betulinic acid (9), butyrospermol (10), euphol (11), betulin aldehyde (12), 2,2-dimethyl-5-hydroxy-7-phenyl-chromane (13), 6-deoxyisojacareubin (14), padiaxanthone (15) and betulonic acid (16). This is the first report of the identification of compounds 5, 6 and 10 in the family, the first report of compounds 14 and 15 in the genus, and the first report of compounds 2, 3, 7, 8, 12, 16 in the species. Chemotaxonomic significance of these compounds is described herein. 相似文献
19.
J.Grant Buchanan Allan R. Edgar Micahel J. Power Gavin C. Williams 《Carbohydrate research》1977,55(1):225-238
2,3,5-Tri-O-benzyl-D-ribofuranosyl bromide (17) has been converted into methyl 3-(2,3,5-tri-O-benzyl-β-d-ribofuranosyl)propiolate (8) and its α anomer 10 in 21 and 42% yields, respectively, by reaction with the silver salt of methyl propiolate. Attemps to prepare 8 from (β-d-ribofuranosyl)ethyne (1) by standard methods were unsuccesful. The reactions of the esters 8 and 10 and the ethyne 1 with several 1,3-dipoles have been examined. With diazomethene, 8 and 10 gave the pyrazole esters 20 and 28, respectively, whereas the ethyne 1 reacted more slowly to give a mixture of 23 (37%) and 26(31%). The ester 10 was converted into the triazoles 32 (51%) and 36 (34%) by reaction with benzyl azide. Treatment of the ester 10 with phenylhydrazine gave the pyrazolone 38 in 71% yield. A number of the products of dipolar addition have been converted into new d-ribofuranosyl-pyrazoles and -triazoles by hydrogenolysis. 相似文献
20.
Chemical investigation of the EtOAc extract of the plant-associated fungus Alternaria alternate in rice culture led to the isolation of a novel liphatic polyketone, alternin A (1), a new indole alkaloid (8), and a new sesquiterpene (11), together with 12 known compounds. Their structures were elucidated by the interpretation of extensive spectroscopic data, and the absolute configurations of 1–3 were established using calculations of ECD spectra, NMR data, and optical rotation values. Compound 1 possesses an unprecedented C25 liphatic polyketone skeleton. Compounds 5 and 10 exhibited potential cytotoxic activities against MCF-7 and HepG cells, and compounds 2, 7, and 9 exhibited potential neuroprotective activities in glutamate induced-PC12 injured cells. 相似文献