An efficient synthesis of quinoxaline derivatives from 4-chloro-4-deoxy-alpha-D-galactose and their cytotoxic activities

A novel and efficient method for the synthesis of quinoxaline derivatives has been developed. Isopropylidenation of 4-chloro-4-deoxy-alpha-D-galactose with 2,2-dimethoxypropane, followed by selective hydrolysis, afforded 2,3-O-isopropylidene-4-chloro-4-deoxy-D-galactose di-methyl acetal (3) as a sole product. Oxidation of compound 3 with (Bu3Sn)2O-Br2 gave corresponding hex-5-ulose derivative in high yields. The hex-5-ulose derivative reacted with o-phenylenediamines under neutral conditions to afford quinoxaline derivatives in reasonable yields. The in vitro cytotoxic activities of these quinoxaline derivatives were investigated.     

Synthesis and evaluation of cytotoxic activities of new guanidines derived from carbazoles

Several new alkylguanidines derived from carbazole have been synthesized in a simple one-pot reaction starting from 3-aminocarbazole derivatives. The aminocarbazoles were reacted with ethoxycarbonylisothiocyanate, to give thiourea intermediates, followed by the addition of an alkylamine and HgCl₂ to give ethoxycarbonylguanidine intermediates. The reaction mixture was then heated at 160 °C to give the N-(1,4-dimethyl-9H-carbazol-3-yl)-N′-alkylguanidines.The cytotoxic activity of all the synthesized guanidines was evaluated against different cell lines.     

Synthesis and cytotoxic activities of 6-chloro-7-arylamino-5,8-isoquinolinediones.

6-Chloro-7-arylamino-5,8-isoquinolinediones were newly synthesized and evaluated for in vitro cytotoxic activities against five human solid tumor cell lines. Among them, 5b, 5c and 5d exhibited potent activities against the cell lines HCT-15 and SK-MEL-2.     

Synthesis of cholestane saponins as mimics of OSW-1 and their cytotoxic activities

To fulfill the structure-activity relationship (SAR) of OSW-1, and aim at finding the simplest structural part while maintaining most of the biological activities, six cholestane saponins were synthesized by introducing OSW-1 disaccharide (2-O-4-methoxybenzoyl-β-d-xylopyranosyl-(1→3)-2-O-acetyl-α-l-arabinopyranosyl) and its 1→4-linked analogue to the 7-hydroxy or 16-hydroxy of steroidal sapogenins. Cytotoxic activities of the products were tested. Compounds 1 and 3 exhibited potent cytotoxicities against five types of human tumor cells, with minimum IC₅₀ of 2.0 and 75 nM, respectively. And due to its high activity and easy accessibility compound 1 could be a potential candidate for new anti-tumor agents.     

Synthesis and biological evaluation of chalcones and their derived pyrazoles as potential cytotoxic agents

A series of substituted chalcones and their corresponding pyrazoles were synthesized and evaluated for in vitro cytotoxic activity against a panel of human cancer cell lines. Out of 93 compounds screened, 8 compounds, 1s, 3i,j,n, 4i,j,n and 4s, showed marked activity. Compounds 4j,n and 4s were found to be the most promising in this study. SAR is also discussed.     

Synthesis and cytotoxic activities of 4,5-diarylisoxazoles

A series of 4,5-diarylisoxazoles related to combretastatin A-4 (CA-4) were synthesized and evaluated for cytotoxicity against three human cancer cell lines. Among them, compound 6e showed better cytotoxic activity than CA-4 in HeLa and HepG2 cell lines assayed with IC(50) value as low as 0.022 and 0.065nM, respectively.     

Four new steroidal glycosides from Solanum torvum and their cytotoxic activities

Two novel C-22 steroidal lactone saponins, namely solanolactosides A, B (1, 2) and two new spirostanol glycosides, namely torvosides M, N (3, 4) were isolated from ethanol extract of aerial parts of Solanum torvum. Their structures were characterized as solanolide 6-O-[α-l-rhamnopyranosyl-(1 → 3)-O-β-d-quinovopyranoside] (1), solanolide 6-O-[β-d-xylopyranosyl-(1 → 3)-O-β-d-quinovopyranoside] (2), yamogenin 3-O-[β-d-glucopyranosyl-(1 → 6)-O-β-d-glucopyranoside] (3) and neochlorogenin 3-O-[β-d-glucopyranosyl-(1 → 6)-O-β-d-glucopyranoside] (4) on the basis of spectroscopic analysis. The cytotoxicities of the saponins (1-4) were evaluated in vitro against a panel of human cancer cell lines. Compounds 3 and 4 showed significant cytotoxic activity with the cell lines.     

Three new cucurbitane triterpenoids from Hemsleya penxianensis and their cytotoxic activities

Two new cucurbitane glycosides, hemslepenside A (1) and 16,25-O-diacetyl-cucurbitacin F-2-O-β-d-glucopyranoside (3), one new cucurbitacin, 16-O-acetyl-cucurbitacin F (2), along with three known cucurbitane compounds, were isolated from the roots of Hemsleya penxianensis. The structures of 1–6 were established on the basis of extensive spectroscopic and chemical methods. The isolated compounds were evaluated for their cytotoxic activities against different three human cancer cell lines, with IC₅₀ values in the low microgram range.     

Four new triterpenoidal saponins from Ilex cornuta and their cytotoxic activities

Four new triterpenoidal saponins (1–4), oleanolic acid 3β-O-α-l-arabinopyranosyl-(1 → 2)-β-d-glucuronopyranoside-6-O-butyl ester (1), oleanolic acid 3β-O-[α-l-arabinopyranosyl-(1 → 2)-β-d-glucuronopyranoside-6-O-butyl ester]-28-O-β-d-glucopyranoside (2), 19α-hydroxy oleanolic acid 3β-O-β-d-glucuronopyranoside-6-O-methyl ester (3), and 19α-hydroxy urs-12-en-28-oic acid 3β-O-α-l-arabinopyranosyl-(1 → 2)-β-d-glucuronopyranoside-6-O-methyl ester (4) were isolated from the roots of Ilex cornuta. Their structures were determined by means of extensive spectroscopic analyses (IR, ESIMS, HRESIMS, 1D and 2D NMR). Compounds 1–9 were tested for their cytotoxic activities by MTT assay, and 1, 3, 5 and 6 showed moderate cytotoxic activities against HeLa, SMMC-7721, and HL-60 human tumor cell lines.     

Synthesis of novel 4'-C-methyl-pyrimidine nucleosides and their biological activities

Two novel 4'-C-methylnucleosides, 4'-methylBVDU 9 and 4'-methylBVaraU 10, were synthesized. The former was derived from 3',5'-di-O-acetyl-2'-deoxy-4'-C-methyluridine 12, and the latter was produced via glycosylation between 4-C-methyl-D-ribose derivative 11 and a silylated bromovinyl uracil. 4'-MethylBVDU 9 exhibited particularly potent anti-varicella-zoster virus (VZV) activity in vitro.     

Steroidal glycosides from the bulbs of Bessera elegans and their cytotoxic activities

Examination of the bulbs of Bessera elegans (Liliaceae) led to isolation of nine new and five known steroidal glycosides. The structures of the nine compounds were determined based on the results of spectroscopic analysis, including two-dimensional NMR, and hydrolysis followed by chromatographic and spectroscopic analysis. The isolated compounds and derivatives were evaluated for cytotoxicity against HL-60 human promyelocytic leukemia cells, A549 human lung adenocarcinoma cells, and TIG-3 normal human diploid fibroblasts. One compound, the pseudo-furostanol glycoside, induced apoptosis in HL-60 and A549 cells in a time-dependent manner and cell-cycle arrest at the G0/G1 phase in A549 cells.     

Diterpenoids from the root bark of Jatropha curcas and their cytotoxic activities

Three new diterpenoids, named epi-jatrophol (1), jatrophaldehyde (2) and epi-jatrophaldehyde (3), along with nine known ones (4–12), were isolated from the root bark of Jatropha curcas. The new compounds were identified by spectroscopic data, and their relative configurations were confirmed by X-ray crystallography or chemical methods. The cytotoxic activities of the isolated compounds were evaluated against HEPG2 and LOVO tumor cell lines. Compounds 8, 9 and 10 were found to be cytotoxic toward HEPG2 cells for the first time.     

Synthesis of resveratrol analogues, and evaluation of their cytotoxic and xanthine oxidase inhibitory activities

Thirteen resveratrol (=5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol) analogues with a CHO group have been prepared by partial synthesis from resveratrol. The synthesized compounds have been evaluated for their cytotoxic activity against a human nasopharyngeal epidermoid tumor cell line KB, as well as for their xanthine oxidase inhibitory activity. Compounds 2, 3, and 6a showed the most significant cytotoxic activities against the cell line KB, and compound 2 also exhibited strong xanthine oxidase inhibitory activity.     

Iridoids and lignans from Valeriana officinalis L. and their cytotoxic activities

Two new iridoids (1 and 2), one new lignan (3) together with one known iridoid (4) and twelve known lignans (5－16) were obtained from the roots of Valeriana officinalis L. (V. officinalis). The structures were determined using IR, MS, ¹D and ²D NMR spectroscopy and the absolute configurations of the new structures were deduced by ECD experiments. All of the isolated compounds were assayed for their cytotoxic activities against three tumour cell lines (A549, HCT116 and SW620) and the results showed that compounds 9 and 10 showed cytotoxicities against A549 cells, compounds 9 and 11 showed cytotoxicities against SW620 cells and compound 10 showed cytotoxicities against HCT116 cells.     

Synthesis of new morpholine-connected pyrazolidine derivatives and their antimicrobial,antioxidant, and cytotoxic activities

A simple and convenient one-pot four-component synthesis of morpholine-connected pyrazolidine derivatives 2a–f and 4a–f was developed using direct metal-free catalysis, with the identities of the synthesized compounds confirmed by IR, NMR (¹H and ¹³C), mass spectrometry, and elemental analysis. The prepared compounds were inspected for antimicrobial, antioxidant, and cytotoxic activities.Antimicrobial and antifungal activities against five bacterial and four fungal pathogens, respectively, were investigated using the disc diffusion technique. In antibacterial activity, compounds 2d and 2f (MIC = 2 μg/mL) exhibited significantly higher activity than the standard ciprofloxacin. The results of antifungal assay showed that the activity of compound 4a (MIC = 0.5 μg/mL) was significantly higher than the standard clotrimazole. Antioxidant activity was screened based on ABTS⁺ radical scavenging and linoleic acid peroxidation performance. Compound 4a showed substantial antioxidant (91.3%) activities, as compared with the Trolox standard. Cytotoxicity was evaluated using HepG2 (liver), HeLa (cervical), and MCF-7 (breast) cancer cell lines, with high toxicities observed for 2b (GI₅₀ = 12.2 μm) and 4a (GI₅₀ = 07.8 μm).     

Synthesis and cytotoxic activities of usnic acid derivatives

Nine usnic acid-amine conjugates were evaluated on murine and human cancer cell lines. The polyamine derivatives showed significant cytotoxicity in L1210 cells. Their activities appeared to be independent of the polyamine transport system (PTS). Indeed, their activities were similar in chinese hamster ovary (CHO) and in the PTS deficient CHO-MG cells. In addition, alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor known to indirectly enhance the activity of the PTS and consequently increase the cytotoxicity of cytotoxic drugs entering cells via the PTS, had no effect on the activity of the polyamine derivatives. The more active derivative (1,8-diaminooctane derivative) displayed similar activities on all cancer cell lines studied and induced apoptosis.     

Synthesis and cytotoxic activities of novel phenacylimidazolium bromides

A series of novel phenacylimidazolium derivatives, bearing an aryl or alkyl substituent at position-1 and a phenacyl substituent at position-3 of the imidazole ring, has been prepared and evaluated in vitro against a panel of human tumor cell lines. Phenacylimidazolium bromides bearing a highly sterically hindered aryl group at position-1 and an electron-rich phenacyl or naphthylacyl substituent at position-3 of imidazole ring proved to be more active than imidazolium bromides with other substituted groups. In particular, compound 5j was found to be the most potent compounds with IC₅₀ values lower than 5.0 μM against 8 strains human tumor cell lines and more active than cisplatin (DDP).     

Synthesis of ring-substituted 4-aminoquinolines and evaluation of their antimalarial activities

A simple two-step synthesis method was used to make 51 B-ring-substituted 4-hydroxyquinolines allowing analysis of the effect of ring substitutions on inhibition of growth of chloroquine sensitive and resistant strains of Plasmodium falciparum, the dominant cause of malaria morbidity. Substituted quinoline rings other than the 7-chloroquinoline ring found in chloroquine were found to have significant activity against the drug-resistant strain of P. falciparum W2.     

Novel cytotoxic bufadienolides derived from bufalin by microbial hydroxylation and their structure-activity relationships

Microbial transformation was used to prepare novel cytotoxic bufadienolides. Twelve products (3-14) were obtained from bufalin (1) by the fungus Mucor spinosus. Their structures were elucidated by high-resolution mass spectroscopy (HR-MS) and extensive NMR techniques, including 1H NMR, 13C NMR, DEPT, 1H-1H correlation spectroscopy (COSY), two dimensional nuclear Overhauser effect correlation spectroscopy (NOESY), heteronuclear multiple quantum coherence (HMQC), and heteronuclear multiple bond coherence (HMBC). Compounds 3, 4, 9 and 11-14 are new mono- or dihydroxylated derivatives of bufalin with novel oxyfunctionalities at C-1beta, C-7beta, C-11beta, C-12beta and C-16alpha positions. The in vitro cytotoxic activities against human cancer cell lines of 3-14, together with 16 biotransformed products derived from cinobufagin (15-30) were determined by the MTT method, and their structure-activity relationships (SAR) were discussed.     

Steroidal saponins and ecdysterone from Asparagus filicinus and their cytotoxic activities

Two new spirostanoides, filiasparosides E (1) and F (2), one new furostanoside, filiasparoside G (3), and one new ecdysterone, stachysterone A-20, 22-acetonide (4), together with six known steroidal saponins, asparagusin A (5), filiasparoside A (6), filiasparoside B (7), aspafilioside A (8), aspafilioside B (9), and filiasparoside C (10) were isolated from the roots of Asparagus filicinus Buch.-Ham. Their structures were elucidated on the basis of spectroscopic and chemical evidence. Compounds 1-10 were investigated for their cytotoxicities against human breast adenocarcinoma MDA-MB-231 cell line and compounds 8-10 exhibited cytotoxic activities with IC₅₀ values ranging from 3.4 to 6.6 μM.