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Carbohydrates have played an important role in organic synthesis. Since they contain many stereocenters, they have been widely used as chiral-pool starting materials. Herein, we report the asymmetric formal synthesis of (–)-swainsonine, which exhibits anticancer and immunosuppressive activities and inhibits lysosomal α-mannosidase activity, from d-mannose and d-arabinose. The synthesis utilized Zn-mediated Bernet–Vasella reaction, Horner–Wadsworth–Emmons olefination, and Grubbs olefin metathesis as key reactions.

Clausena excavata, a shrub in the Rutaceae family, has been used in traditional medicine to alleviate cold, malaria, abdominal pain, bacterial infection, and HIV infection. The major biologically active constituents in the rhizomes and roots of C. excavata are the three pyranocoumarins; clausenidin, dentatin, and nordentatin. Due to the medicinal values of this plant, we have developed a quick and convenient qHNMR method to quantify clausenidin, dentatin, and nordentatin from the rhizomes and roots of C. excavata collected from six geographical locations throughout Thailand. The dried and powdered samples were extracted with deuterated methanol. The parameters for 1H NMR measurements were optimized according to the measured T1 relaxation time of the protons from the bioactive pyranocoumarins and of 2,3,5,6-tetrachloronitrobenzene (TCNB), the internal standard. HPLC assays were also conducted to verify the results obtained from the qHNMR method. The amount of clausenidin, dentatin, and nordentatin varied from different geographical locations, and the results from the qHNMR method were comparable to those obtained from the HPLC assays. The reported qHNMR method was quick, more convenient, and more applicable to large-scale quality control or screening than conventional HPLC methodology. The method developed herein is beneficial to the pharmaceutical and health industries.

The asymmetric total synthesis of (−)-epiquinamide has been achieved starting from a 5-iodofuranoside synthon derived from d -glucose. The methods featured Bernet-Vasella reaction followed by Horner-Wadsworth-Emmons (HWE) reaction to provide a new chiral building block diene as the key steps. The bicyclic framework of this quinolizidine was constructed by selective reduction of α,β-unsaturated ester, intramolecular nucleophilic substitution and ring-closing metathesis.

Plasmodium proteases play both regulatory and effector roles in essential biological processes in this important pathogen and have long been investigated as drug targets. Plasmepsin V from P. falciparum (PfPMV) is an essential protease that processes proteins for export into the host erythrocyte and is a focus of ongoing drug development efforts. In the present study, recombinant protein production, inhibition assays, binding studies as well as molecular docking and molecular dynamics simulation studies were used to investigate the mode of binding of a PEXEL-based peptidomimetic and naphthoquinone compounds to PfPMV. Consistent with our previous study, refolded PfPMVs were produced with functional characteristics similar to the soluble counterpart. Naphthoquinone compounds inhibited PfPMV activity by 50% at 50 μM but did not affect pepsin activity. The IC50 values of compounds 31 and 37 against PfPMV were 22.25 and 68.94 μM, respectively. Molecular dynamics simulations revealed that PEXEL peptide interacted with PfPMV active site residues via electrostatic interactions while naphthoquinone binding preferred van der Waal interactions. P1′-Ser of the PfEMP2 substrate formed an additional H-bond with Asp365 promoting the catalytic efficiency. Additionally, the effect of metal ions on the secondary structure of PfPMV was examined. Our results confirmed that Hg2+ ions reversibly induced the changes in secondary structure of the protein whereas Fe3+ ions induced irreversibly. No change was observed in the presence of Ca2+ ions. Overall, the results here suggested that naphthoquinone derivatives may represent another source of antimalarial inhibitors targeting aspartic proteases but further chemical modifications are required.

The total synthesis of (+)-epiquinamide and (−)-epiepiquinamide has been achieved starting from a 3,5-dihydroxyfuranoside synthon derived from d -mannose. The methods featured Bernet-Vasella reaction followed by Horner-Wadsworth-Emmons (HWE) reaction to provide a new chiral building block diene as the key steps. The bicyclic framework of this quinolizidine was constructed by using ring-closing metathesis, selective reduction of ester and intramolecular nucleophilic substitution-cyclization.

Carbohydrates, inexpensive chiral sources, are very useful for many syntheses of chiral bioactive compounds. We have chosen to synthesize benzyl α- d -mannofuranosides and d -lyxofuranosides with dioxolane-type, 2,3-O-isopentylidene and 2,3-O-benzylidene acetals from d -mannose. Interestingly, we have discovered new knowledge about the cleavage of dioxolane-type using two catalysts, Cu(OTf)2/BH3·THF and TiCl4/Et3SiH. The results showed that the regioselectivity of the benzylidene acetal ring opening was affected by the adjacent hydroxy (OH) group and was not directed by the stereochemistry of the acetal center. The substrates containing OH groups at position 5 can be cleaved by Cu(OTf)2/BH3·THF in tetrahydrofuran to exclusively provide the 2-O-benzyl-3-hydroxy compounds. When the substrates bore the OH group at position 6, using TiCl4/Et3SiH in dichloromethane gave a similar pattern. If the substrates lacked the OH group at position 5 or 6, the reactions did not proceed or gave low selectivity. Our discovery is very useful for dioxolane-type ring opening of carbohydrate synthesis.

The facile synthesis of a partially protected OSW-1 disaccharide moiety, having a 2-O-p-methoxybenzoyl-β-D-xylopyranosyl-(1 → 3)-2-O-acetyl-L-arabinopyranoside structure, was elaborated by glycosylation in a β-stereoselective fashion. The xylopyranose donors were synthesized by a short synthetic approach via convenient selective 1,2-diacetal protection of 3,4-trans-diequatorial hydroxyl group. Regioselective ring opening of 1,2-diacetal-protected substrates efficiently led to the arabinopyranose acceptor with a free 3-hydroxyl group. Glycosylation of the xylopyranose donor with the arabinopyranose acceptor provided the β-disaccharide.

Numerous naphthoquinone derivatives, such as rhinacanthins function as anticancer drugs, which target hTopoII. The structure of hTopoII contains both an ATPase domain and a DNA binding domain. Several drugs bind to either one or both of these domains, thus modifying the activity of hTopoII. The naphthoquinone esters and amides used in this study showed that their hTopoIIα inhibitory activity was inversely proportional to ATP concentration. In order to better characterize the inhibitory action of these compounds, sufficient quantities of soluble functional hTopoII-ATPase domain were required. Therefore, both the alpha and beta isoforms of the hTopoII-ATPase domain were over-expressed in Escherichia coli. The hTopoIIα-ATPase activity was reduced in the presence of naphthoquinone derivatives. Additionally, a molecular docking study revealed that the selected naphthoquinone ester and amide bind to the ATP-binding domain of hTopoIIα. Collectively, the results here provide for the first time a novel insight into the interaction between naphthoquinone esters and amides, and the ATP-binding domain of hTopoIIα. The further elucidation of the mechanism of action of the naphthoquinone esters and amides inhibitory activity is essential.

Carbohydrates, inexpensive chiral sources, are very useful for many syntheses of chiral bioactive compounds. We have chosen to synthesize benzyl α- d -mannofuranosides and d -lyxofuranosides with dioxolane-type, 2,3-O-isopentylidene and 2,3-O-benzylidene acetals from d -mannose. Interestingly, we have discovered new knowledge about the cleavage of dioxolane-type using two catalysts, Cu(OTf)2/BH3·THF and TiCl4/Et3SiH. The results showed that the regioselectivity of the benzylidene acetal ring opening was affected by the adjacent hydroxy (OH) group and was not directed by the stereochemistry of the acetal center. The substrates containing OH groups at position 5 can be cleaved by Cu(OTf)2/BH3·THF in tetrahydrofuran to exclusively provide the 2-O-benzyl-3-hydroxy compounds. When the substrates bore the OH group at position 6, using TiCl4/Et3SiH in dichloromethane gave a similar pattern. If the substrates lacked the OH group at position 5 or 6, the reactions did not proceed or gave low selectivity. Our discovery is very useful for dioxolane-type ring opening of carbohydrate synthesis.

A short and practical synthesis of oseltamivir phosphate was accomplished in 11 steps from inexpensive and abundant starting material, d -mannose. This synthetic route featured an intramolecular Horner–Wadsworth–Emmons reaction as the key step to furnish the cyclohexene ring product. The hydroxyl group was converted stereo specifically into an amino group by oxidation to the ketone and reductive amination whereas the second amino group was introduced by azide substitution of a hydroxyl group. This synthesis provided an economical and practical alternative for the synthesis of Tamiflu.

Dioxolane type 3,4-benzylidene acetals of benzyl β- l -arabinose either as a mixture or pure exo- and endo -isomers cleavaged with BF 3 ·OEt 2 /Et 3 SiH in dichloromethane or acetonitrile regioselectively, provided the 4- O -benzyl-3-hydroxy derivative. The reaction with TiCl 4 /Et 3 SiH or Cu(OTf) 2 /Et 3 SiH provided a mixture of 3- and 4- O -benzyl derivatives whereas with Cu(OTf) 2 /BH 3 ·THF gave only hydrolyzed product. The regioselectivity of the reaction was proved to be directed by the acetyl substitution at C-2. Benzyl substitution provided a mixture of 3- and 4- O -benzyl derivatives in 1:1 ratio whereas non-substitution yielded the same mixture in 2:1 ratio.

Twelve novel naphthoquinone esters containing cyclopentyl and cyclohexyl substituents at C-2' of the propyl chain were synthesized by starting from 1-hydroxy-2-naphthoic acid via alkylation with cyclopentyl ester and cyclohexyl ester. They were evaluated for cytotoxicity against three cancer cell lines (human epidermoid carcinoma (KB), human cervical carcinoma (HeLa), and human hepatocellular carcinoma (HepG(2))). In comparison to naphthoquinone esters with the 2',2'-dimethyl group, the naphthoquinones with a 2'-cyclopentyl substituent showed stronger activity than those with a 2'-cyclohexyl substituent, but less than that with the 2',2'-dimethyl group. This work provides new information about the effect of 2'-position substituents on the cytotoxicity of naphthoquinone ester analogues.

A series of new polyoxygenated steroid derivatives with various steroid skeleton moieties were synthesized. Antitumor activity of the compounds against three tumor cell lines (Breast cancer MCF7, lung cancer NCI and oral cancer KB) were evaluated. Compounds with aromatic A ring of this series exhibited the most potent cytotoxicities in all tested cells. The absence of OH at C-16 or lack of cholesterol like side chain at C-20 in the steroid skeleton apparently result in decreased cytotoxicity. The compound became inactive when the side chain contains double bond at C-24-C-25. When hydroxyl group at C-3 was protected no cytotoxicities against MCF7 and NCI and considerable low cytotoxicity against KB cell lines were observed.

Twenty-six novel naphthoquinone aliphatic esters were synthesized by esterification of 1,4-naphthoquinone alcohols with various aliphatic acids. The 1,4-naphthoquinone alcohols were prepared from 1-hydroxy-2-naphthoic acid in nine steps with excellent yields. Twenty-four of the novel synthetic naphthoquinone esters showed significant antimalarial activity with IC(50) values in the range of 0.03-16.63 microM. The length of the aliphatic chain and the presence of C-2' substituents on the propyl chain affected the activity. Interestingly, compounds 31 and 37 showed very good antimalarial activity and were not toxic to normal Vero cells, and the PTI values of 31 (>1990.38) and 37 (1825.94) are excellent. Both 31 and 37 showed potent inhibition against P. falciparum 3D7 cyt bc(1) and no inhibition on rat cyt bc(1). They showed IC(50) values in the nanomolar range, providing full inhibition of cyt bc(1) with one molecule inhibitor bound per cyt bc(1) monomer at the Q(o) site.

Using tigogenin as starting material, (20 S )-20-hydroxycholestane-3,6-dione ( 1 ), (16 S , 20 S )-16,20-dihydroxycholestan-3-one ( 2 ), (20 S )-20-hydroxycholest-1-ene-3,16-dione ( 3 ) and (20 S )-20-hydroxycholest-4-ene-3,16-dione ( 4 ), natural polyoxygenated steroids from the gorgonian, Leptogorgia sarmentosa , were synthesized in four steps. Antitumor activity against three tumor cell lines (breast cancer, MCF7, lung cancer NCI and oral cancer KB) was evaluated. Two compounds ( 3 and 4 ) showed strong activity against NCI (IC 50 6.16 and 10.51 μM) and moderate activity against MCF7 and KB, the IC 50 being in the range 30.65–47.22 μM. Compound 2 showed moderate activity against NCI (IC 50 42.68 μM) but was inactive against MCF7 and KB whereas compound 1 showed no activity against all tested cells.

In a screening for small-molecule compounds that alleviate the deleterious effects of external CaCl(2) on zds1 Delta strain yeast, we found 2-((1-(hydroxymethyl) cyclohexyl) methyl) naphthalen-1-ol (NKH-7) to be an active compound. NKH-7 also inhibited cell growth at higher concentrations. To identify its target in growth inhibition, we isolated NKH-7-resistant mutants and selected those mutants that exhibited dominant or semi-dominant resistance specifically to NKH-7. By gene cloning, a TUB1 mutant gene encoding alpha-tubulin with a Ser248Pro mutation was identified. Deletion of the TUB3 gene, a minor gene encoding alpha-tubulin, led to supersensitivity to NKH-7. Cellular tubulin-containing arrays as visualized by green fluorescent protein (GFP)-labeled alpha-tubulin diminished rapidly on exposure to the inhibitor. The mutation was situated proximal to the alpha-beta interface of alpha-tubulin in microtubule protofilaments, suggesting the possibility that NKH-7 affects the hydrolysis of GTP bound to beta-tubulin. A functional connection perhaps exists between the tubulin inhibition and Ca(2+)-dependent cell-cycle regulation.

Physiological regulation of laccase production from Ganoderma sp. KU-Alk4, isolated in Thailand, was controlled by the initial glucose concentration in liquid culture. Different laccase isozymes were produced using different starting concentrations of glucose. With 1% glucose, two isozymes, KULac 1 and 2 were produced, while with 4% glucose, three different isozymes, KULac 3, 4 and 5, were produced. The KULacs differed in their molecular mass, ranging from 53 to 112 kDa. KULac 2 was a new laccase that had a different N-terminal amino acid sequence from other laccases previously reported. All the isozymes had optimum pH at 3.5 and were stable over the wide range of pH, 3.0–10.0, especially in alkaline pH. It is noteworthy that the activities of the four KULacs with 2,6-dimethoxyphenol were extremely high up to 90°C. They retained 100% of their activities at 60°C for 1 h.

Total synthesis of isagarin (2) has been accomplished in five steps with 24.1% overall yield from 2‐bromonaphthoquinone (6). The key step is a palladium‐catalyzed cyclization to form a bicyclic ketal ring.

Palladium catalysed 3-component cascades are described involving aryl/heteroaryl iodides, allene and benzyl malononitrile. Catalytic monohydration and monoamination of malononitriles to the corresponding monoamides and monoamidines are also described together with several examples of mono-oxazoline formation.

A cholesterol model compound, containing 16β‐acetoxy, 17α‐hydroxy, and (20S, 22R)‐epoxy groups was synthesized from diosgenin in 13 steps and was rearranged regio‐ and stereo‐specifically to an orthoester with BF3·Et2O.

Amphibian skin has been the source of a wide variety of biologically active substances, but less than one-third of the known genera of amphibians have been probed for such active substances. Skins of 21 genera of anurans from Thailand have now been investigated for noxious secretions, toxic substances, and alkaloids. Four genera of bufonid toads (Bufo, Ansonia, Leptophryne, Pedostipes) were toxic due to the presence of bufadienolides or bufadienolide-like compounds. Two species of ranid frogs (Rana raniceps, Rana signata) were toxic, perhaps due to the presence of toxic peptide(s). Two species of rhacophorid frogs (Polypedates) were slightly noxious/toxic. One species of microhylid frog (Kaloula pulchra) was noxious. Trace amounts of pumiliotoxin alkaloids were detected in a ranid frog (Limnonectes kuhli). A further 18 species did not exhibit noxious or toxic properties to a significant extent.

Rhinacanthin-M, -N and -Q, natural products isolated from the medicinal plant Rhinacanthus nasutus, and 39 novel naphthoquinone esters have been synthesized in excellent yield by esterification of naphthoquinone-3-(propan-3'-ols) with benzoic or naphthoic acids. Almost all the naphthoquinone esters that contain a C-3 hydroxy group showed significant cytotoxicities against KB, HeLa, and HepG2 cell lines. In contrast, ester derivatives lacking the C-3 hydroxy group were inactive to the cancer cell lines. Two methyl substituents on the C-2' of propyl chain conferred more potent cytotoxicity than when there is only one or no methyl group. Naphthoate esters exhibited greater cytotoxicity than benzoate esters. Computer modeling has been done to obtain a first look at the mode of action in connection with these observations.

Rhinacanthone (1) and two 1,2-pyranonaphthoquinones (2,3) were synthesized and found to show very potent cytotoxicity against three cancer cell lines (KB, HeLa and HepG(2)) with IC(50) values of 0.92-9.63 microM, whereas the corresponding hydroxylated derivative 4 had reduced cytotoxicity (IC(50) values of 7.61-24.13 microM). Three 1,2-furanonaphthoquinone derivatives (5-7) were also synthesized with similar cytotoxicity as 1,2-pyranonaphthoquinones. In comparison to 1,2-naphthoquinones, six 1,4-naphthoquinones derivatives fused with pyran ring (8-10) and furan ring (11-13) were synthesized and they showed less cytotoxicity or inactive to the cancer cell lines. Moreover, compound 13 had significant cytotoxicity against HeLa cell line (IC(50) value of 9.25 microM) while it showed no toxic to vero cell.

The first syntheses of 16β-chloro- and 16β-bromo-cyproterone acetate is described. The preparation of 16β-chlorocyproterone acetate was accomplished in eight steps (6.5% overall yield) from commercially available 16-dehydropregnenolone acetate. 16β-Bromocyproterone acetate was prepared from 16β-chlorocyproterone acetate with base-induced epoxide formation as the key step.

The anti-influenza drug, oseltamivir phosphate (Tamiflu) was synthesized from d-glucose via a novel and efficient synthetic route. A unique feature of the synthesis is that the key intermediate aziridine cyclohexene was synthesized as a mixture of diastereomers, via a metal-mediated domino reaction and ring closing metathesis (RCM). The iodoxylose compound was prepared in 9 steps from d-glucose. Both isomers of aziridine cyclohexene intermediate could be converted into Tamiflu via two pathways. First, both isomers of aziridine cyclohexene underwent aziridine-ring opening yielded diastereomeric of 1,2-amino mesylate cyclohexene esters. The trans-1,2-amino mesylate isomer could be transformed to tamiflu by formation of aziridine then regio- and stereoselective nucleophilic substitution of the azide to afford 1,2-amino azido compound whereas the cis-isomer could be transformed directly by SN2 substitution of azide to give the same azido product, which then converted into oseltamivir phosphate.

This report describes the isolation of two triterpenes from the stems of Tinospora crispa, namely, cycloeucalenol (1). and cycloeucalenone (2). for the first time. It was found that cycloeucalenol (1). slightly increased the right atrial force of contraction whereas it showed an initial reduction followed by sustained reduction of about 10% on the left atria of the rat in vitro. Cycloeucalenone showed slight change from the control on the right and left atrial force. These results suggest that cycloeucalenol and cycloeucalenone produced mild cardiotonic effects.

The facile synthesis of a partially protected OSW-1 disaccharide moiety, having 2-O-p-methoxybenzoyl-β-D-xylopyranosyl-(1 → 3)-2-O-acetyl-L-arabinopyranoside structure, was elaborated by glycosylation in a β-stereoselective fashion. The xylopyranose donors were synthesized by a short synthetic approach via convenient selective 1,2-diacetal protection of 3,4-trans-diequatorial hydroxyl group. Regioselective ring opening of 1,2-diacetal-protected substrates efficiently led to the arabinopyranose acceptor with a free 3-hydroxyl group. Glycosylation of the xylopyranose donor with the arabinopyranose acceptor provided the β-disaccharide.

A 3-step 100% atom economic sequence is reported whereby a variety of phenols react with 2 mol equiv. of allene to give phenoxymethyl-1,3-dienyl ethers. Subsequent thermal Claisen rearrangement to C-1,3-dienes and acid catalysed ring closure furnishes 3:1–6.5:1 mixtures of exo -methylene chromans and dihydrobenzofurans with the former predominating.

An efficient synthesis of the influenza neuraminidase inhibitor prodrug oseltamivir phosphate (Tamiflu) from cheap, commercially available d -ribose is described. The main features of this approach comprise a metal (Zn, In)-mediated domino reaction and ring-closing olefin metathesis (RCM) of the resultant functionalized dienes to produce the Tamiflu skeleton. The synthesis described in this Letter represents a new and efficient transformation of a shikimic acid derivative into a 1,2-diamino compound which involved oxidation of an alcohol followed by reductive amination, regioselective ring opening of an amino pentylidene ketal and stereospecific nucleophilic replacement of a triflate with an azide.

The described transformation tolerates a broad variety of functional groups and uses ammonium tartrate as a novel ammonia surrogate.

Catalytic 5-component cascade chemistry provides an effective stereo- and regioselective route to novel multi-functional Z,Z-bisallylamines. The process, which is capable of considerable further extension, utilises ammonium tartrate as a novel ammonia source which avoids the use of ammonia gas or aqueous ammonia.

Fourteen new naphthoquinone aliphatic amides and seventeen naphthoquinone aliphatic esters were synthesized in nine to ten steps from 1-hydroxy-2-naphthoic acid with 9-25% overall yield for the amides, and 16-21% overall yield for the esters. The key step of the amide synthesis is a coupling reaction between amine and various aliphatic acids using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) as a coupling agent while for the ester synthesis, DCC/DMAP or CDI was used as the coupling reagent between aliphatic acids and naphthoquinone alcohol. Both naphthoquinone amides and esters were evaluated for their anticancer activity against KB cells. It was found that naphthoquinone aliphatic amides showed stronger anticancer activity than those of the esters when the chains are longer than 7-carbon atoms. The optimum chain of amides is expected to be 16-carbon atoms. In addition, naphthoquinone aliphatic esters with α-methyl on the ester moiety possessed much stronger anticancer activity than the straight chains. Decatenation assay revealed that naphthoquinone amide with 16-carbon atoms chain at 15 μM and 20 μM can completely inhibit hTopoIIα activity while at 10 μM the enzyme activity was moderately inhibited. Molecular docking result also showed the same trend as the cytotoxicity and decatenation assay.

Starting from 1-hydroxy-2-naphthoic acid, a series of novel naphthoquinone aromatic amides is synthesized by a new route using Fremy′s salt oxidation and tBu-OOH/TritanB hydroxylation as the key steps.

Clausenidin, O-methylmukonal, 3-formyl-2,7-dimethoxycarbazole, and clauszoline-J, isolated from the rhizomes and roots of Clausena excavata, exhibit anti-HIV-1 activity in a syncytial assay with EC(50) values of 5.3, 12.0, 29.1, and 34.2 microM, respectively. Due to the highly active anti-HIV-1 property, quantitative analysis of four compounds are investigated. The direct analysis of these four compounds in the crude extracts of the combined rhizomes and roots of Clausena excavata from ten various sources in Thailand by high-performance liquid chromatography is accomplished. Chromatographic separation is achieved on a C(18) column, and the mobile phase is a mixture of methanol and distilled water in a mode of isocratic or gradient elution detected at 254 nm at a flow rate of 0.6 mL/min for clausenidin, at 274 nm at a flow rate of 0.6 mL/min for O-methylmukonal, at 298 nm at a flow rate of 0.4 mL/min for 3-formyl-2,7-dimethoxycarbazole, and at 242 nm at a flow rate of 0.4 mL/min for clauszoline-J. This is the first quantitative analysis of these four anti-HIV-1 compounds from the crude extract without prior isolation and purification steps.

In an effort to determine the pharmaceutical utility and the structural requirements for activity against tumor cell lines, 30 novel 9,11-secosterol analogues with different side chains and degrees of oxidation at C-9 were synthesized starting from hecogenin. Evaluation of the synthesized compounds for cytotoxicity against KB, HeLa and MCF-7 cell lines revealed that some important structural features are required for activity. The presence of a cholesterol-type side chain, which appears to play a major role in determining the biological activity, the existence of a ketone functional at C-9 is also crucial for anticancer activity whereas hydroxyl/ketone function at C-22 on the side chain did not increase cytotoxicity.

Clausena excavata Burm. f. (Rutaceae) is a medicinal plant which is used in folklore medicine for treatment of cold, malaria, AIDS, dermatopathy, abdominal pain, and snake-bite. This plant is a rich source of coumarins and carbazole alkaloids. So far, fifty-three coumarins and fifty-eight carbazole alokaloids were isolated from C. excavata. Furthermore, a small group of tetranortriterpenoids, steroids, flavonoids, and essential oils were also obtained from this plant. C. excavata showed diverse therapeutic activities which are antibacterial, antifungal, antiplatelet, antiplasmodial, antitumor, antinociceptive, immunomodulatory, antimycobacterial, and anti-HIV-1 activities. The incidence of HIV-1 infection leading to AIDS has increased every year, and fungal and bacterial infections, particularly TB-causing mycobacteria are prevalent in HIV-infected patients. So Clausena excavata which showed inhibition of these diseases, is very promising to be developed for treatment of AIDS.

Upon searching plant extracts for inhibitors of the Ca(2+) signaling pathway using the zds1Delta-yeast proliferation based assay, a crude rhizome extract of Boesenbergia pandurata was found to be strongly positive, and from this extract pinostrobin, alpinetin, and pinocembrin chalcone were isolated as active components. Further biochemical experiments confirmed that pinostrobin possesses inhibitory activity on the Ca(2+) signals involved in the control of G2/M phase cell cycle progression in Saccharomyces cerevisiae.

Rhinacanthone, a main bioactive naphthoquinone, isolated from roots of Rhinacanthus nasutus KURZ, (family Acanthaceae), a Thai traditional medicine, has been reported to possess anticancer effects, although the anticancer mechanism is still unclear. Therefore, we investigated the effects of rhinacanthone on cell proliferation, cell cycle progression and apoptosis induction in human cervical carcinoma (HeLa) cells. beta-Lapachone, an anticancer drug having a chemical structure related to rhinacanthone, was used as a positive control. The results demonstrated that rhinacanthone inhibited proliferation of HeLa cells in a dose-dependent manner and had greater efficacy than that of beta-lapachone: IC(50) values of the compound ranged from 1.2+/-0.1 to 5.5+/-0.86 muM for 2-24 h time periods. Rhinacanthone-treated HeLa cells displayed several apoptotic features as evidenced by the appearance of chromatin condensation, internucleosomal DNA fragmentation, increase in the proportion of sub G(1) apoptotic cells, and externalization of annexin-V. The apoptotic processes by the treatment with rhinacanthone involved in a marked increase in the level of pro-apoptotic protein Bax and decrease in the levels of anti-apoptotic proteins Bcl-2 and survivin as well as subsequent activation of caspase-9 and caspase-3. Moreover, rhinacanthone increased the expression of apoptosis-inducing factor (AIF) which would translocate from mitochondria to nucleus through cytosol, and induce apoptosis through caspase independent signaling pathway. Taken together, our findings for the first time demonstrate that rhinacanthone-induced apoptosis in HeLa cells is mediated primarily through the mitochondria-dependent signaling pathway, suggesting that it may be a promising agent for the treatment of human cervical cancer.

Eight novel 2-(2'-cyclopentyl)- and 2-(2'-cyclohexyl) substituted 1-naphthol derivatives were synthesized in good yield starting from 1-hydroxy-2-naphthoic acid. Two of them, 2-((1-(hydroxymethyl)cyclopentyl)methyl)naphthalene-1-ol (8) and 2-((1-(hydroxymethyl)cyclohexyl)methyl)-naphthalene-1-ol (9) showed anticyclooxygenase activity on COX-2 with IC(50) values of 19.90 microM and 7.77 microM, respectively and 9 also inhibited COX-1 (5.55 microM), while the other six were inactive on both isozymes. Molecular docking experiments indicated that the orientation of the active naphthols is different from that of the inactive ones. Two evidences playing important roles for the inhibition by the active compounds, are 1) C-1 and C-3' hydroxyl groups formed hydrogen bonds with COX-2/COX-1 Val523/Ile523 and Arg120, respectively, 2) hydrogen at C-5 of the naphthalene nucleus was attracted rather close to the phenolic group of Tyr385 due to van der Waals interaction.

Three carbazole derivatives, O-methylmukonal (1), 3-formyl-2,7-dimethoxycarbazole (2) and clauszoline J (3), and a pyranocoumarin, clausenidin (4), were isolated from the rhizomes and roots of Clausena excavata. Compound 1, isolated from this plant for the first time, has not been reported previously as having anti-HIV-1 activity. Compounds 1–4 displayed anti-HIV-1 activity in a syncytial assay with EC50 values of 12, 29.1, 34.2 and 5.3 µm, respectively, and thus exhibited potential therapeutic index (PTI) values of 56.7, 8.0, 1.6 and 7.0, respectively. All isolated compounds demonstrated a lack of cytotoxicity against the KB and BC-1 cancer cell lines. Copyright © 2005 John Wiley & Sons, Ltd.

A limonoid, clausenolide-1-ethyl ether (1) and two coumarins, dentatin (2) and nor-dentatin (3), were isolated from Clausena excavata. Limonoid 1 was obtained from the crude ethanol extract of the rhizomes and the roots but had not previously been isolated from C. excavata and exhibited HIV-1 inhibitory activity. Coumarins 2 and 3, with their structures related to an anti-HIV-1 substance, (+)-calanolide A (4), were obtained from the crude chloroform extract of the rhizomes. Both induced toxicity to cells used in a syncytium assay for anti-HIV-1 activity. These compounds, 1–3, did not show any cytotoxic effect against KB and BC-1 cell lines (IC50 value > 20 µg/mL). Copyright © 2003 John Wiley & Sons, Ltd.

The first syntheses of 16β-chloro- and 16β-bromo-cyproterone acetate is described. The preparation of 16β-chlorocyproterone acetate was accomplished in eight steps (6.5% overall yield) from commercially available 16-dehydropregnenolone acetate. 16β-Bromocyproterone acetate was prepared from 16β-chlorocyproterone acetate with base-induced epoxide formation as the key step.

An effective method for synthesis of 16α-methyl cyproterone acetate was accomplished starting from commercially available 16-dehydropregnenolone acetate in eight steps, 11.5% overall yield.