A novel cycloartane glycoside fromThalictrum uchiyamai

A new cycloartane glycoside (1) was isolated from the aerial part ofThalictrum uchiyamai Nakai (Ranunculaceae). On the basis of chemical and physicochemical evidence, the aglycone structure of this compound was characterized as 16,25-dihydroxy-3,24-diacetoxy-9, 19-cycloartane-29-oic acid, a new derivative of cycloartane triterpene. Also, the oligosaccharide moiety of this glycoside were determined as 29-O-α-L-rhanmnopyranosyl-(1→2)-[β-D-xylofuranosyl-(1→6)]-β-D-glucopyranosy by application of HMBC technique. Consequently, the structure of compound 1 was elucidated as 29-O-α-L-rhanmnopyranosyl-(1→2)-[β-D-xylofuranosyl-(1→6)]-β-D-glucopyranosyl-16, 25-dihydroxy-3,24-diacetoxy-9,19-cycloartane-29-oic acid ester.     

Anti-Candida,docking studies,and in vitro metabolism-mediated cytotoxicity evaluation of Eugenol derivatives

The high morbidity and mortality rates of Candida infections, especially among immunocompromised patients, are related to the increased resistance rate of these species and the limited therapeutic arsenal. In this context, we evaluated the anti-Candida potential and the cytotoxic profile of eugenol derivatives. Anti-Candida activity was evaluated on C. albicans and C. parapsilosis strains by minimum inhibitory concentration (MIC), scanning electron microscopy (SEM), and molecular docking calculations at the site of the enzyme lanosterol-14-α-demethylase active site, responsible for ergosterol formation. The cytotoxic profile was evaluated in HepG2 cells, in the presence and absence of the metabolizing system (S9 system). The results indicated compounds 1b and 1d as the most active ones. The compounds have anti-Candida activity against both strains with MIC ranging from 50 to 100 μg ml⁻¹. SEM analyses of 1b and 1d indicated changes in the envelope architecture of both C. albicans and C. parapsilosis like the ones of eugenol and fluconazole, respectively. Docking results of the evaluated compounds indicated a similar binding pattern of fluconazole and posaconazole at the lanosterol-14-α-demethylase binding site. In the presence of the S9 system, compound 1b showed the same cytotoxicity profile as fluconazole (1.08 times) and compound 1d had 1.23 times increase in cytotoxicity. Eugenol and other evaluated compounds showed a significant increase in cytotoxicity. Our results suggest compound 1b as a promising starting point candidate to be used in the design of new anti-Candida agent prototypes.     

Flavonoid glycosides from leaves and straw of Oryza sativa and their effects of cytotoxicity on a macrophage cell line and allelopathic on weed germination

Five new flavonoids namely, 5-hydroxy-6-isoprenyl-7,4′-dimethoxyflavonol-3-O-β-d-arabinofuranoside (1), 5,7-dihydroxy-4′-methoxyflavone-7-O-β-d-arabinopyranosyl-2′′-n-decan-1′′′-oate (2), 3-butanoyl-5,6,8-trihydroxy-7,4′-dimethoxyflavonol--5-O-β-d-glucopyranoside (3), 7, 4′-dimethoxy-5-hydroxyflavone-5-O-α-d-arabinopyranosyl-(2′′?→?1′′′)-O-α-d-arabinopyranoside (4), and 5,6-dihydroxy-7, 4′-dimethoxyflavone-5-O-α-d-glucopyranoside (5), together with two known compounds, were isolated from the methanol extract of Oryza sativa leaves and straw. Their structures of new compounds were elucidated by 1D and 2D NMR spectral methods, viz: COSY, HMBC and HSQC aided by mass techniques and IR spectroscopy. The cytotoxicity of these compounds (1–7) were assessed by using (RAW 264.7) mouse macrophages cell line, and allelopathic effects of compounds (1–7) on the germination characteristics of barnyardgrass (Echinochloa oryzicola) and pigweed (Chenopodium album L.) were also evaluated. The compounds 1, 6 and 7 showed cytotoxicity and compounds 1–7 exhibited significant inhibitory activity on the seed germination of two weed species.     

南酸枣的黄烷类成分及其体外抗肿瘤与抗缺氧活性

目的 阐明南酸枣Choerospondias axillaries (Roxb.) Burtt. et Hill.树皮中黄烷类成分及其体外抗肿瘤、抗缺氧、抗菌活性。方法 利用各种色谱技术分离化学成分,根据理化性质和波谱数据鉴定结构,利用MTT法测评抗肿瘤及抗缺氧活性,采用纸片法测定抗菌活性。结果 从南酸枣树皮中分离鉴定了3个黄烷类化合物 (+)-儿茶素（1）、(+)-儿茶素-7-O-β-D-吡喃葡萄糖苷（2）和 (+)-儿茶素-4’-O-β-D-吡喃葡萄糖苷（3）。化合物1、2 对K562细胞呈一定的抗肿瘤活性,在100.mL^-1质量浓度下的抑制率分别为16.0%和27.3%。在ECV304细胞缺氧损伤保护实验中,化合物1在无细胞毒作用的50 μg.mL^-1质量浓度下呈较强的抗缺氧活性,化合物3未表现出抗肿瘤与抗缺氧活性。化合物1~3在测试浓度下对受试白色念珠菌和金黄色葡萄球菌无抗菌活性。结论 化合物1为南酸枣抗缺氧活性成分的首例报道,其抗缺氧活性也属首次报道。化合物2和3为首次从该属植物中分离得到。     

Chemical constituents from the fruiting bodies of <Emphasis Type="Italic">Cryptoporus volvatus</Emphasis>

New drimane-type sesquiterpene cryptoporol A (1), cryptoporic acid derivative 6′-cryptoporic acid E methyl ester (2), and pseudouridine derivative cryptoporine A (3), as well as a known ergosterol 5α,8α-epidioxy-22E-ergosta-6,22-dien-3β-ol (4), were isolated from a 90 % alcohol extract of the fruiting bodies of Cryptoporus volvatus. The structures of these compounds were established by spectroscopic analysis and circular dichroism. 5α,8α-epidioxy-22E-ergosta-6,22-dien-3β-ol (4) exhibited antiviral activity against porcine reproductive and respiratory syndrome virus, and all compounds showed weak antioxidant activities.     

Palladium(II) imine ligands cyclometallated complexes with a potential leishmanicidal activity on Leishmania (L.) amazonensis

The leishmaniasis, considered a neglected disease, is caused by a protozoan from the genus Leishmania. There is an urgent need to search for safer, cheaper, and more effective treatments against leishmaniasis. In this context, transition metal complex activities have been studied, as palladium, which has become an interesting alternative as metal-based drugs. In this study, three new palladium(II) complexes, obtained from two imine ligands, were synthesized and characterized by elemental analyses, infrared and ¹H NMR spectroscopies. The in vitro evaluation of ligands and complexes has been tested on promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and its cytotoxicity on murine macrophages. All complexes exhibited a leishmanicidal activity on promastigotes and amastigotes forms. The ligands activities were improved after coordination with palladium, and the replacement by some substituents has increased the leishmanicidal activity even more. Complexes with chloride and thiocyanate showed an improvement of activity when compared to their respective ligands, with better selectivity index (SI > 1) and less damage on mammalian cells when compared to a reference drug pentamidine. These compounds are promising agents for leishmaniasis treatment, and the results emphasize the potential properties of compounds with transition metal for medical applications.     

Synthesis of some 5′-amino-2′,5′-dideoxy-5-iodouridine derivatives and their antiviral properties against herpes simples virus

In an attempt to improve the antiviral efficacy of 5′-amino-2′,5′-dideoxy-5-iodouridine (AIdU) the N-acetyl and N,3′-O-diacetyl derivatives were prepared. N-Acetylation of AIdU increased its ability to inhibit the phosphorylation of thymidine by the deoxypyrimidine kinase of herpes simplex virus type 1 (HSV1) while diacetylation had the converse effect. The affinity of the corresponding compounds containing uracil or thymine for virus deoxypyrimidine kinase was also determined. A range of N-acyl-, N-sulphonyl- and N,3′-O-diacyl- derivatives of AIdU were synthesised; enhanced inhibition of deoxypyrimidine kinase by a number of these compounds was observed. The previous observation that 5′-azido-2′,5′-dideoxy-5-iodouridine has antiherpetic activity in vivo led us to investigate its 3′-O-acetyl derivative as well as the corresponding compound containing uracil. None of the derivatives described showed antiviral activity in cell culture against HSV1; acylation failed to enhance the potency of AIdU against HSV1 in vivo.     

Cycloartane triterpenes from Beesia calthaefolia and their anticomplement structure–activity relationship study

Fifteen cycloartane triterpenes were isolated from Beesia calthaefolia and among them one was new cycloartane triterpenoid. The structure of new compound was determined by the application of spectroscopic analyses and chemical methods. The fifteen compounds were evaluated for their anticomplement activity by classic pathway. The structure–activity relationship analysis indicated that the configurations of 12-OH is preferable to be α than β, and 18-OH can decrease while 15-OH can increase the anticomplement activity, but saponin with both 15-OH and 18-OH lost most of its activity. The glycosyl moiety of most isolated cycloartane triterpenes is xylosyl. When xylosyl was substituted by glucosyl or galactosyl, their anticomplement activities were decreased or increased, respectively. Further structure–activity relationship (SAR) studies must be carried out to achieve general conclusions regarding the effect of further functionalizations on the anticomplement saponins.     

升麻甙F的分离和结构

升麻甙Ｆ的分离和结构李从军，李英和，肖培根（中国医学科学院，中国协和医科大学药用植物资源开发研究所北京１０００９４）升麻属（Ｃｉｍｉｃｉｆｕｇａ）植物是毛莨科升麻族植物（Ｃｉｍｉｃｉｆｕｇｅａｅ，ｓ．１．）的主要成员，但在化学成分上，以其特征性成分环...     

Cycloartane-type triterpene glycosides from Beesia calthaefolia and their anticomplement activity

Two new 9,19-cycloartane triterpenes (1, 2), together with three known compounds (3–5), were isolated from the whole plant of Beesia calthaefolia. Their structures were determined by the application of spectroscopic analyses and chemical methods. Compound 1 showed moderate anticomplement activity similar to that of the positive control (rosmarinic acid), while compounds 3 and 4 showed weak activity. The results suggest that 6′-O-(4″-hydroxy-3″-methoxy-benzoyl)-β-d-glucosyl of 9,19-cycloartane-type triterpenoids could be a structure that is essential for anticomplement activity.     

Synthesis of new series of pyrimido[4,5-b][1,4] benzothiazines as 15-lipoxygenase inhibitors and study of their inhibitory mechanism

A series of 2-substituted 4-n-propyl pyrimido[4,5-b][1,4]benzothiazines were synthesized, and evaluated as soybean 15-lipoxygenase (SLO) inhibitors. Among the synthesized compounds, 2-(4-methyl piperazinyl) analog showed the best SLO inhibition activity (IC₅₀ = 8.9 ± 0.4 μM). To rationalize the inhibitory potency variation of the compounds, computer-assisted modeling of the enzyme-inhibitor, radical scavenging evaluation, and inhibitory mechanism analyses were performed. The results showed that in 4-alkyl pyrimido[4,5-b]benzothiazines with same 2-substituent, radical scavenging potency plays a key role in lipoxygenase inhibition.     

Synthesis and cytotoxic evaluation of some new[1,3]dioxolo[4,5-g]chromen-8-one derivatives

Background

Homoisoflavonoids are naturally occurring compounds belong to flavonoid classes possessing various biological properties such as cytotoxicity. In this work, an efficient strategy for the synthesis of novel homoisoflavonoids, [1,3]dioxolo[4,5-g]chromen-8-ones, was developed and all compounds were evaluated for their cytotoxic activities on three breast cancer cell lines.

Methods

Our synthetic route started from benzo[d][1,3]dioxol-5-ol which was reacted with 3-bromopropanoic acid followed by the reaction of oxalyl chloride to afford 6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one. The aldol condensation of the later compound with aromatic aldehydes led to the formation of the title compounds. Five novel derivatives 4a-e were tested for their cytotoxic activity against three human breast cancer cell lines including MCF-7, T47D, and MDA-MB-231 using the MTT assay.

Results

Among the synthesized compounds, 7-benzylidene-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4a) exhibited the highest activity against three cell lines. Also the analysis of acridine orange/ethidium bromide staining results revealed that 7-benzylidene-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4a) and 7-(2-methoxybenzylidene)-6,7-dihydro-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4b) induced apoptosis in T47D cell line.

Conclusion

Finally, the effect of methoxy group on the cytotoxicity of compounds 4b-4d was investigated in and it was revealed that it did not improve the activity of [1,3]dioxolo[4,5-g]chromen-8-ones against MCF-7, T47D, and MDA-MB-231.     

New cycloartane glycosides from the rhizomes of Cyperus rotundus and their antidepressant activity

Two new cycloartane glycosides, cyprotusides A (1) and B (2), were isolated from the rhizomes of Cyperus rotundus. Their chemical structures were elucidated on the basis of IR, MS, NMR spectroscopic analyses coupled with chemical degradation. The potential antidepressant activity of the two compounds was evaluated. In the despair mice models, compounds 1 and 2 showed significant antidepressant activity.     

Substituted 2-[(2-Oxo-2H-[1,2,4]triazino [2,3-c]quinazolin-6-yl)thio]acetamides with Thiazole and Thiadiazole Fragments: Synthesis,Physicochemical Properties,Cytotoxicity, and Anticancer Activity

The series of novel N-R-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)thio]acetamides with thiazole and thiadiazole fragments in a molecule were obtained by alkylation of potassium salts 1.1–1.4 by N-hetaryl-2-chloroacetamides and by aminolysis of activated acids 2.1–2.4 with N,N’-carbonyldiimidazole (CDI). The structures of compounds were determined by IR, ¹H NMR, MS, and EI-MS analysis. The results of cytotoxicity evaluated by the bioluminescence inhibition of bacterium Photobacterium leiognathi, Sh1 showed that the compounds have considerable cytotoxicity. The synthesized compounds were tested for anticancer activity in NCI against 60 cell lines. Among the highly active compounds 3.1, 3.2, and 6.5, 2-[(3-methyl-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)thio]-N-(1,3-thiazol-2-yl)acetamide (3.1) was found to be the most active anticancer agent against the cell lines of colon cancer (GI₅₀ at 0.41–0.69 μM), melanoma (GI₅₀ 0.48–13.50 μM), and ovarian cancer (GI₅₀ 0.25–5.01 μM). The structure-activity relationship (SAR-analysis) was discussed.     

Synthesis and evaluation of the trypanocidal activity of a series of 1,3,4-thiadiazoles derivatives of <Emphasis Type="Italic">R</Emphasis>-(+)-limonene benzaldehyde-thiosemicarbazones

In this study, we synthesized a series of 1,3,4-thiadiazole derivatives of R-(+)-limonene benzaldehyde-thiosemicarbazones (2a–k). We also determined the cytotoxicity in LLCMK₂ cells and the activity against epimastigote and trypomastigote forms of Trypanosoma cruzi, of these synthetic compounds and also of a series of 1,3,4-thiadiazole without the monoterpene R-(+)-limonene (4a–k). 1,3,4-Thiadiazole compounds showed significant trypanocidal activity and a high selectivity indexes. The vast majority of the monoterpene derivatives, substituted by R-(+)-limonene, presented better anti-T. cruzi activity than the non-substituted compounds. Regarding the cytotoxic profile, the compounds without the monoterpene R-(+)-limonene were, in general, less toxic. The present findings indicate that the 1,3,4-thiadiazoles derivatives of R-limonene have potential trypanocidal activity that justify further studies to better understand the mechanism of action of these substances on T. cruzi.     

Synthesis of azabicyclo[4.2.0]octa-1,3,5-trien-8-one analogues of 1H-imidazo[4,5-c]quinoline and evaluation of their antimicrobial and anticancer activities

In search of new and efficient antimicrobial and anticancer agents based on the imidazoquinoline structural framework, a series of novel 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-ones (8a–f) were synthesized from the corresponding 2,4-dihydroxoquinoline derivative through multistep reactions. The structures of these compounds were established by IR, ¹H NMR, ¹³C NMR and mass spectral studies. The 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-one (8a–f) analogues were evaluated for their in vitro antimicrobial activity by serial dilution method minimum inhibitory concentration (MIC). The derivatives 8c, 8e and 8f exhibited excellent antibacterial activity comparable to the parent drug ampicillin with MIC value. Compounds 7a–f and 8a–f were also assessed for their cytotoxic activity (IC₅₀) against HeLa cells using the Trypan blue exclusion assay method. The compounds 7c and 8b displayed potential anticancer activity. In a molecular docking study, these compounds showed minimum binding energy and good affinity towards the active pocket. They are believed to be good inhibitors of β-tubulin. The results of these studies provided evidence that 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-one (8a–f) derivatives are a promising class of antibacterial and anticancer agents.     

Multicomponent synthesis of pyrido[2,3-a]carbazoles and cytotoxic activity

Pyrido[2,3-a]carbazoles were synthesized by multicomponent reactions using l-proline as catalyst. All the newly synthesized compounds were characterized by all spectral means. The in-vitro cytotoxicity of the newly synthesized pyrido[2,3-a]carbazoles was evaluated by SRB (sulforhodamine B) assay against MCF-7 (Breast Cancer), HeLa (cervix adenocarcinoma), and A549 (Human Lung adenocarcinoma). Cisplatin, a clinically used antitumor agent was also evaluated for standard. All the newly synthesized pyrido carbazoles showed moderate to good cytotoxic activity and their structural activity relationship has been established.     

Anticancer activity of some [1,2,4]triazepino[2,3-<Emphasis Type="Italic">a</Emphasis>] quinazoline derivatives: monolayer and multicellular spheroids in vitro models

In this study, five derivatives of triazepino[2,3-a] quinazoline-2,7(1H)-dione were synthesized and their anticancer activities were investigated both in two-dimensional-monolayer and three-dimensional-multicellular spheroids cancer models. All the five compounds showed very high anticancer activities against the 11 cancer cell types that have been investigated in the monolayer model. Comparing the results of both monolayer and multicellular spheroids models of the anticancer activity of these five compounds, we can conclude that the meta-methyl derivative induced its anticancer activity through apoptosis to give the best results in the monolayer model. However, in the multicellular spheroids model its apoptotic activity induced moderate anticancer activity (64?% cytotoxicity). On the other hand, both two nitro-derivatives either in meta-position or para-position, did not show potent pro-apoptotic activities toward the monolayer model but showed very high cytotoxic activity toward the multicellular spheroids model (100?%). These results reveal that the cell death mechanism induced by both nitro-compounds is exerted via other path than the apoptosis. Interestingly, all the tested compounds were generally safe to normal cells spheroids when tested at the same concentration.     

[1,2,4]Triazolo[4,3-a]quinoxaline: synthesis, antiviral, and antimicrobial activities

A series of novel [1,2,4]triazolo[4,3-a]quinoxaline derivatives and their isosteres, pyrimido-quinoxaline, were synthesized as potential antiviral and antimicrobial agents. The new compounds were synthesized via aromatic nucleophilic substitution of 4-chloro-8-methyl[1,2,4]triazolo[4,3-a]quinoxaline-1-amine with different amines and triazole-2-thiol. Some of the synthesized compounds were subjected to antiviral and cytotoxicity screening using plaque-reduction assay. Most of the tested compounds exhibited cytotoxicity at concentration 160?μg/ml and compound 8b showed promising antiviral activity. In vitro antimicrobial screening against different pathogenic organisms using agar diffusion method demonstrated that compounds 4d, 6c, 7b, and 8a exhibit antibacterial and/or antifungal activities.     

Chemical constituents of Isodon nervosus and their cytotoxicity

Two new ent-kaurane diterpenoids, 6,20,15α-trihydroxy-6,7-seco-1α,7-olide-ent-kaur-16-ene (1) and 7β,12α-dihydroxy-6β,15β-diacetoxy-7α,20-epoxy-ent-kaur-2,16-dien-1-one (2), together with the six known compounds, were isolated from the aerial part of Isodon nervosus. The structures of the new compounds were determined by spectral methods (1D, 2D NMR, and MS). Six compounds were assayed for their cytotoxicity against HL60, SMMC-7721, and HeLa human cell lines. Compounds 5, 7, and 8 showed significant cytotoxicity.