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Eight new alkaloids, which are four new tetrahydroprotoberberine alkaloids, stephapierrines A–D (1–4), and four new aporphine alkaloids, stephapierrines E–H (5–8), together with three new naturally occurring alkaloids (9–11) and thirty-four known alkaloids (12–45) were isolated from the tubers of Stephania pierrei Diels. The structures of the new compounds were elucidated by spectroscopic analysis and physical properties. The structures of the known compounds were characterized by comparison of their spectroscopic data with those previously reported. Compound 42 exhibited the strongest acetylcholinesterase (AChE) inhibitory activity, which was more active than galanthamine, the reference drug. Compound 23 showed the highest butyrylcholinesterase (BuChE) inhibitory activity, which was also more active than galanthamine. Molecular docking studies are in good agreement with the experimental results.

Two new haemanthamine-type alkaloids, crinasiaticine A (1) and crinasiaticine B (2), along with fifteen known alkaloids 3–17, were isolated from the bulbs of Crinum asiaticum L. var. asiaticum. The structures of the new compounds were established by spectroscopic analysis and the known compounds were identified by spectral comparison with those previously reported. All of the compounds were evaluated for their inhibitory potential against human carbonic anhydrase isozyme II (hCAII) in vivo activity using a novel yeast-based assay. Compounds 5 and 15 inhibited hCAII activity with minimal effective doses of 166 and 8.7 μM, respectively. These two compounds did not show cytotoxicity, even at the high concentration used.

The present study was performed to examine the antihypertensive effect of neferine in hypertensive rats and its relaxant mechanisms in isolated rat thoracic aorta. The antihypertensive effect was evaluated by tail-cuff methods on NG-nitro-L-arginine methyl ester (L-NAME) (40 mg/kg BW) 4-week hypertensive-induced hypertensive rats. The vasorelaxant effect and its mechanisms were studied by the organ bath technique in the thoracic aorta isolated from normotensive rats. The results indicated that the treatment of neferine (1 mg/kg and 10 mg/kg) markedly decreased the systolic blood pressure (SBP) when compared with the hypertension group (137.75 ± 10.14 mmHg and 132.23 ± 9.5 mmHg, respectively, p

Five new triterpenoid saponin glycosides, trichocucumerisides A–E (1–5), together with eleven known compounds (6–16) were isolated from Trichosanthes cucumerina fruit fibers. The structures of the new compounds were elucidated by detailed analysis of NMR and mass spectroscopic data as well as chemical reactions. The anti-inflammatory study against nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells shows that compounds 7 and 9 exhibited stronger NO inhibitory activity, with IC50 values of 3.0 and 2.7 μM, respectively, with comparison to positive references Celecoxib and aminoguanidine (IC50 values 75.7 and 75.0 μM, respectively). Compounds 7 and 9 also possessed a greater selectivity index (SI) of approximately 3–4-fold activity than that of the positive references.

Six new isopimarane diterpenes, marginaols A-F (1-6), along with eight known compounds (7-14), were isolated from the rhizomes of Kaempferia marginata. The structures and absolute configurations of 1-6 were established on the basis of spectroscopic methods and the experimental and calculated ECD data as well as comparison with the literature values. Most of the isolated compounds were tested for their nitric oxide (NO) inhibitory effects in lipopolysaccharide-activated RAW264.7 cells. Among them, marginaol B (2) was found to reduce NO levels in murine macrophage cells with an IC50 value of 28.1 ± 1.7 μM.

A new long chain, multifidione (1), together with seven known lathyrane-type diterpenes, 15-epi-4Z-jatrogrossidentadion (2), 4Z-jatrogrossidentadion (3), 2-epi-hydroxy isojatrogrossidentadion (4), 2-hydroxyisojatrogrossidentadion (5), 4E-jatrogrossidentadion (6), 15-epi-4E-jatrogrossidentadion (7), and jatrogrossidion (8), was isolated from the roots of Jatropha multifida L. The chemical structure of this new compound was elucidated by spectroscopic techniques. The known compounds were identified by comparison of the spectroscopic and physical data with those of reported values. The isolated all compounds were evaluated for herpes simplex type-1 (HSV-1). Among them, compound 6 showed the highest activity against HSV-1 (IC50 2.05 μg/mL), whereas the IC50 value of the standard drug, acyclovir, was 3.58 μg/mL. These results suggest that compound 6 may has a potential target for anti-HSV-1 drug development.

[Image: see text] Cucurbitacin B (CuB), a highly cytotoxic constituent of the Cucurbitaceae plant, was identified to exhibit potent inhibitory activity against human cancer cells as well as normal cells. This disadvantage hampers the possibility of developing this compound into an anticancer drug candidate. In this work, several bioreductive prodrugs of CuB were designed to reduce toxicity to normal cells while maintaining the cytotoxic effect to cancer cells. Embedded with a bioreductive delivery and cleavable system in cancer tissues, cucurbitacin B-based prodrugs 1, 2, and 3 were synthesized and evaluated by in vitro and in vivo experiments. Compared with the parent CuB, prodrug 1 was found to significantly reduce the toxicity down to 310-fold lower against noncancerous cells. LC-MS analyses show that prodrug 1 efficiently releases the parent compound in the reductase-overexpressed MCF-7 cells. In addition, prodrug 1 shows satisfactory and comparable effectiveness in controlling tumor growth as that by tamoxifen in the 4T1 xenograft mice model.

β-Thalassemia is the major health problems in developing countries, when affected patients and healthy carriers are numerous, resulting a total absence or severe decrease in the production of β-globin chains. The use of chemical agents for increasing the production of fetal hemoglobin (HbF) by reactivating γ-globin gene to balance excess α-globin chains is an alternative therapeutic approach. Therefore, the search for molecules exhibiting the property of inducing γ-globin gene expression is of great interest. In this report, we discovered that quercetin (1), the major flavonoid isolated from the heartwoods of the medicinal plant Anaxagorea luzonensis promoted the expression of γ-globin gene. Chemical modification of 1 to fourteen methyl ether analogs (2−15) was conducted. The structures of these compounds were established on the basis of their spectroscopic data and by comparison with those of the reported values. The parent flavonoid and its chemically modified analogs were investigated for their γ-globin gene induction for the first time. The parent compound 1 exhibited less induced γ-globin gene expression than cisplatin and hemin, the positive controls. 3,4′-Di-O-methylquercetin (7), the modified analog, significantly enhanced γ-globin gene expression with 2.6-fold change at 8 μM, which was slightly higher than cisplatin and hemin. Moreover, compounds 1 and 7 displayed less cytotoxic activity against K562::ΔGγAγEGFP cells than cisplatin. Structure-activity relationship (SAR) study revealed that the methoxyl groups at the 3- and 4ʹ-positions and the free hydroxyl group at the 7-position are required for strong HbF-inducing activity.

Diarylheptanoid, 1-(4-hydroxyphenyl)-7-phenyl(6E)-6-hepten-3-one (HPPH), has been reported to enhance myoblast differentiation via estrogen receptor (ER). However, the underlying signaling pathway promising this action remains unknown. The present study thus aimed to investigate the signaling pathway of HPPH that enhances myoblast differentiation. Confluence C2C12 myoblasts were induced to differentiate in the absence or presence of HPPH (10 nM). Differentiation markers (myosin heavy chain (MHC) and myogenin) and other signaling molecules implicated in myogenic differentiation were analyzed by immunostaining and western blotting methods. To identify the location of ER and the signaling molecules, specific inhibitors were applied targeting these molecules. Nuclear factor-κB (NF-κB) DNA binding activity was measured using the electrophoresis mobility shift assay. The results showed that HPPH enhanced myoblast differentiation by increasing MHC and myogenin levels, number, and size as well as the fusion index of myotubes. These actions occurred via membrane ER. Several MAPK proteins were activated at the early stage of differentiation. However, only Akt and p38 MAPK, but not ERK, were implicated in these effects. The underlying signaling molecules of Akt to enhance myogenic differentiation by HPPH, at least in part, were mTOR/P70S6K and GSK-3β. On the other hand, the downstream signaling molecule of p38 MAPK was NF-κB. Our results suggested that HPPH enhanced myogenic differentiation by binding with membrane ER, which in turn recruited multiple axes including Akt-mTOR-P70S6K, Akt-GSK-3β, and p38 MAPK-NF-κB.

Natural tyrosinase inhibitors from herbal plants are promising therapeutic agents for skincare and cosmetic products. Natural curcuminoids exhibit weak antityrosinase properties. The structural modification of curcumin, the major curcuminoid from Curcuma longa, gave 14 analogues. The tyrosinase inhibitory activity of the natural curcuminoids and the modified analogues on both L-tyrosine and DOPA substrates were evaluated. The inhibition kinetics were also undertaken. For analogues with potent activity on the L-tyrosine substrate, the isoxazole analogue 12 and two reduced analogues, hexahydrocurcumin (16) and the α,β-unsaturated analogue 17, showed IC50 values of 8.3, 14.6 and 9.4 µM, and were 20.9-, 11.9- and 18.4-fold more active, respectively, than kojic acid, the reference compound. For the analogues with potent antityrosinase on DOPA substrate, the dimethylated analogue 5 exhibited the strongest antityrosinase activity against the DOPA substrate, with the IC50 value of 8.0 µM, which was 16.6-fold more active than kojic acid. The inhibition kinetics revealed that curcuminoid 5 could bind with both free enzyme and with the enzyme–substrate complex. It acted as a competitive–uncompetitive mixed-II type inhibitor. Curcuminoid 17 could bind with both free enzyme and the enzyme–substrate complex. The results indicated that 17 acted as a competitive–uncompetitive mixed-I type inhibitor, while curcuminoid 12 was a noncompetitive inhibitor which bound with both free enzymes and the enzyme–substrate complex. These potent analogues might serve as new potential tyrosinase inhibitors for the prevention and treatment of skin pigmentation disorders.

Two new series of 19-silylether- and 19-formyl-7-acetyl-12-amino-14-deoxyandrographolide analogues were designed and synthesized from natural andrographolide via key step reactions including allylic hydroxylation, tandem CAE reaction and one pot formylation. Evaluation of their cytotoxicity against eight cancer cells line found 6e exhibited the highest activity on MCF-7 cancer cell (IC50 2.93) and comparable to the drug elipticin. Replacement of silylether at C-19 with formyl group exhibited selective activity on P-388 cell line. Computational studies revealed the amino group at C-12 and O-acetoxy at C-7 position play significant roles in cytotoxicity against MCF-7 cancer cells. Cytotoxicity of these two series highlights the importance of 12-substituted-14-deoxyandrographolide scaffold and these types of compounds could be employed in future developments against breast cancer.

A series of 21 new analogues of C-12 dithiocarbamate andrographolide was designed and synthesized from natural andrographolide isolated from a common Thai plant, Andrographis paniculata. The reaction used to manipulate the andrographolide scaffold was conducted in one pot under mild reaction conditions. This avoided toxic catalysts and gave nearly quantitative yields of new analogues, generally without by-products and can be easily scaled -up for industrial processing. All new analogues were evaluated against nine cancer cell lines, some analogues exhibited greater selective cytotoxic activity to MCF-7 cancer cell than that of the parent andrographolide and cancer drugs.

New iridoid glycoside derivatives from durantoside I, the latter from the dried flowers and leaves of Citharexylum spinosum, were synthesized by variously modifying a sugar moiety by silylation or acetylation and/or removal of cinnamate group at C-7 position and subsequent screening for comparative cytotoxicity against several cancer cell lines. Addition of alkylsilane to durantoside I and removal of cinnamate group were most effective in improving cytotoxicity.

Phosphodiesterase 5 inhibitors have been used as a first-line medicine for the treatment of erectile dysfunction. In the search for new phosphodiesterase 5 inhibitors from natural sources, we found that the 95% ethanol extract of Derris scandens stem showed phosphodiesterase 5 inhibitory activity with an IC50 value of about 7 µg/mL. Seven isoflavones and a coumarin constituent isolated from this plant were investigated for phosphodiesterase 5 inhibitory activity. The results showed that osajin (8), 4′,5,7-trihydroxybiprenylisoflavone (4), and derrisisoflavone A (2) had the ability to inhibit phosphodiesterase 5 with IC50 values of 4, 8, and 9 µM, respectively. These compounds exhibited selectivity on phosphodiesterase 5 over phosphodiesterase 1, however, the selectivity on phosphodiesterase 5 over phosphodiesterase 6 was low. In order to quantitatively determine these bioactive constituents in D. scandens extract, LC-QTOF-MS method has been developed and validated. The limit of quantitation values in the range of 0.1 – 5 µg/mL were obtained. The assay showed satisfactory precision and accuracy. The results from our method showed that the 95% ethanol extract of D. scandens stem was comprised of all eight compounds, with derrisisoflavone A (2) and lupalbigenin (3) presenting as the major constituents.

A method for quantification of diarylheptanoids in Curcuma comosa rhizomes and selected pharmaceutical preparations was established by using HPLC-diode array detector (DAD). The chromatographic separation of three diarylheptanoids [(3S)-1-(3,4-dihydroxy-phenyl)-7-phenyl-(6E)-6-hepten-3-ol (1), (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (2), and (3S)-1,7-diphenyl-(6E)-6-hepten-3-ol (3)] was performed on a Luna C18 analytical column using gradient elution with 0.5% acetic acid in water and acetonitrile with a flow rate of 1 mL/min and a column temperature of 35°C. The calibration curves for the analytes showed good linearity (R2>0.999), high precision (relative standard deviation (RSD)

A series of 1,2,3-triazole-containing Sorafenib analogues, in which the aryl urea moiety of Sorafenib (1) was replaced with a 1,2,3-triazole ring linking a substituted phenoxy fragment, were prepared successfully via Huisgen 1,3-dipolar cycloaddition and nucleophilic aromatic substitution. The studies of cytotoxicity towards human hepatocellular carcinoma (HCC) cell lines, HepG2 and Huh7, indicated that p-tert-butylphenoxy analogue 2m showed significant inhibitory activity against Huh7 with IC50 = 5.67 ± 0.57 µM. More importantly, 2m showed low cytotoxicity against human embryonal lung fibroblast cell line, MRC-5, with IC50 > 100 µM, suggesting its highly selective cytotoxic activity (SI > 17.6) towards Huh7 which is much superior to that of Sorafenib (SI = 6.73). The molecular docking studies revealed that the analogue 2m bound B-RAF near the binding position of Sorafenib, while it interacted VEGFR2 efficiently at the same binding position of Sorafenib. However, 2m exhibited moderate inhibitory activity toward B-RAF, implying that its anti-Huh7 effect might not strictly relate to inhibition of B-RAF. Wound healing and BrdU cell proliferation assays confirmed anti-cell migration and anti-cell proliferative activities towards Huh7. With its inhibitory efficiency and high safety profile, 2m has been identified as a promising candidate for the treatment of HCC.

A series of 14-deoxy-11,12-didehydroandrographolide analogues were synthesized from naturally occurring andrographolide and their cytotoxicity evaluated against nine cancer cell lines including cholangiocarcinoma. Analogues 5a and 5b exhibited the most potent cytotoxicity with ED50s of 3.37 and 3.08 μM on KKU-M213 cell lines and 2.93 and 3.27 μM on KKU-100 cell lines, respectively. Selective cytotoxicity on cholangiocarcinoma cell lines identified in this study highlight the importance of structural modification in the development of drugs for this cancer.

Phytochemical investigation of the CHCl3 extract of the seed embryos of Nelumbo nucifera Gaertn resulted in the isolation of a new naturally occurring bisbenzylisoquinoline alkaloid, O-methylneferine (1), together with five known alkaloids, neferine (2), armepavine (3), (–)-(1R)-N-methylcoclaurine (4), nuciferine (5), and pronuciferine (6). The structures of these compounds were characterized by spectroscopic methods and comparison of physical properties with those reported in the literature. Among them, compounds 1 and 2 exhibited significant activity against human colon adenocarcinoma cell line (HT-29), with IC50 values of 0.70 and 1.61 µM, respectively, which were 8- and 3.5-fold higher than that of the reference anticancer drug, doxorubicin (IC50 5.63 µM). Moreover, compounds 1 and 2 displayed less cytotoxic activity against the non-cancerous HEK 239 cells with the IC50 values of 42.48 and 12.19 μM, respectively, whereas the cytotoxicity of doxorubicin against this cell line was 0.22 μM. The very potent cytotoxicity against HT-29 cell line and very high selectivity index (60.6-fold) of the alkaloid 1 is of particular significant; it could be considered as a promising structure lead for anti-colon cancer drug development.

Important anticancer cytotoxicological properties are reported from synthetic analogs of 14-deoxy-12-hydroxy-andrographolide, a compound that occurs in Andrographis paniculata, an indigenous Southeast Asia plant. Cytotoxicities of 15 synthesized 14-deoxy-12-hydroxy-andrographolide analogs were evaluated against a panel of cancer cell lines with some exhibiting much greater than the parent compound. For example analog 2j was 6–35 times more potent than the parent compound and the anticancer agent, ellipticin, on all cell lines except LU-1 cancer cells. With promising cytotoxicities and simple preparation, this compound has significant potential in the treatment of cancer.

Phytochemical investigation of the stem bark of Xylopia pierrei Hance led to the isolation of one triterpene, polycarpol (1), three heptenes, (7R)-acetylmelodorinol (2), (7R)-melodorinol (3), and melodienone (8), and four flavonoids, pinocembrin (4), isochamanetin (5), chrysin (6), and dichamanetin (7). All compounds were isolated for the first time from this plant species. The structures of the isolated compounds were characterized by spectroscopic techniques and by comparison of the spectroscopic data with the literature values and the stereochemistry at the asymmetric carbon was determined by the modified Mosher’s method. Among them, compound 2 displayed potent cytotoxic activity against human small cell lung cancer (NCI-H187) cells with an IC50 value of 6.66 μM and it was 2.3-fold higher than that of the reference anticancer drug, ellipticine. In addition, compound 2 was also evaluated against the non-cancerous Vero cells and showed high selectivity index of 8.89, which is 59-fold greater than that of ellipticine. The findings suggest that compound 2 should be further developed as a potential lead molecule for anticancer drug development.

Phytochemical investigation of Trigonostemon reidioides roots led to the isolation of fourteen compounds. These included six new diterpenoids, trigonoreidons A−F (1−6), together with eight known diterpenoids 7−14. The structures of the new compounds were elucidated by spectroscopic techniques and the absolute configuration at the asymmetric carbon was determined by the modified Mosher's method. The structure of trigonoreidon B (2) was confirmed by X-ray crystallographic analysis. The known compounds were identified by comparison of the spectroscopic and physical data with those of reported values. The isolated compounds were evaluated for antimycobacterial activity against Mycobacterium tuberculosis. Among the compounds that exhibited antimycobacterial activity, the diterpenoids rediocide C (12) and rediocide G (14) were the most active compounds, with the MIC value of 3.84 μM.

Anti-androgenic drugs are treatments for androgen-related disorders such as benign prostatic hyperplasia, acne, hirsutism, and androgenic alopecia. Germacrone (1), a sesquiterpene isolated from hexane extracts of Curcuma aeruginosa Roxb. rhizome, is an androgen inhibitor of steroid 5-alpha reductase in-vitro. Here, we used the similarity of germacrone's α,ß-unsaturated carbonyl to testosterone's α,ß-unsaturated carbonyl to find germacrene analogs obtained from this plant and by semi-synthesis that might be more potent steroid 5-alpha reductase inhibitors. 8-Hydroxy germacrene B (4) was ~13-fold more potent than its parent, 1 and the most potent (IC50, 0.15±0.022 mM) among 9 compounds tested. The conformation of its cyclodecadiene ring and the α,ß-unsaturated ketone/hydroxy in the germacrene molecule might be crucial role for its anti-androgen activity. Moreover, 1 and 4 showed mild cytotoxic effect on prostate cancer cells. Neither compound was cytotoxic towards human dermal papilla cells at 100 μg/mL. We show that this SAR strategy created promising anti-androgenics for androgen dependent disorders and may create further analogues with further improvements in selectivity and clinical efficacy.

Phytochemical investigation of the roots of Cissampelos pareira Linn. led to the isolation of one new pyrrole alkaloid, cissampeline (1), together with ten known alkaloids, (−)-curine (2), (−)-cyclanoline (3), (+)-tetrandrine (4), (+)-obaberine (5), (+)-obamegine (6), (−)-oblongine (7), (+)-homoaromoline (8), (−)-nor-N׳-chondrocurine (9), trans-N-feruloyltyramine (10) and (+)-coclaurine (11). Their structures were elucidated by extensive NMR and MS spectroscopic analyses. Interestingly, compound 1 represents the first example of pyrrole alkaloid found in the genus Cissampelos. Moreover, compounds 5-11 were isolated for the first time from this genus. Among them, compound 6 showed the highest anti-acetylcholinesterase activity with an IC50 value of 3.26 µM, whereas compound 8 displayed the most potent cytotoxicity against human colon cancer (HT29) cells with an IC50 value of 7.89 µM.

Phytochemical investigation of the roots of Morinda coreia led to the isolation of one new bianthraquinone, morindaquinone (1), together with 12 known compounds, soranjidiol (2), rubiadin-1-methyl ether (3), 2-methoxy-1,3,6-trihydroxyanthraquinone (4), 1-hydroxy-2-methylanthraquinone (5), tectoquinone (6), nordamnacanthal (7), damnacanthal (8), 2-formylanthraquinone (9), 3-hydroxy-2-hydroxymethylanthraquinone (10), lucidin-��-methyl ether (11), scopoletin (12) and (+)-mellein (13). The structures of these compounds were determined on the basis of extensive spectroscopic analyses, as well as by comparison with literature reports. Compound 1 was the first example of bianthraquinone found in the genus Morinda, whereas compound 13 was firstly isolated from this genus. Among them, compounds 2, 7, 8 and 10 exhibited moderate to weak cytotoxicity against human cervical (HeLa), human colon (HT 29) and human breast (MCF-7) cell lines, while compounds 6 and 9 ��� 11 showed weak anti-acetylcholinesterase activity.

Three new oxygenated xanthones, fuscaxanthones L-N (1–3), and 14 known xanthones 4–17, together with the other known metabolites 18–20 were isolated from the stem barks of Garcinia fusca Pierre. Their chemical structures were determined based on NMR and MS spectroscopic data analysis, as well as single X-ray crystallography. The geranylated compounds, cowanin (13), cowagarcinone E (15), norcowanin (16) and cowanol (17) exhibited potent inhibitions against acetylcholinesterase (AChE) (IC50 0.33–1.09 μM) and butyrylcholinesterase (BChE) (IC50 0.048–1.84 μM), which were more active than the reference drug, galanthamine. Compound 15 was highly potent BChE inhibitor (IC50 0.048 μM) and was 76-fold more potent than the drug. Structure-activity relationship studies indicated that the C-2 prenyl and C-8 geranyl substituents in the tetraoxygenated scaffold are important for high activity. Molecular docking studies revealed that the leads 13 and 15–17 showed similar binding orientations on both enzymes and very well-fitted at the double binding active sites of PAS and CAS with strong hydrophobic interactions from both isoprenyl side chains.

Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations. Recent studies revealed that abnormal gene expression induced by epigenetic changes including aberrant promoter methylation plays a critical role in human breast carcinogenesis. Cucurbitacin B has antiproliferative activity against various human breast cancer cells, but the molecular mechanism is not completely understood. In this study, we explore the influence of cucurbitacin B from Trichosanthes cucumerina on the methylation status at the promoter of oncogenes c-Myc, cyclin D1, and survivin in breast cancer cell lines. Growth inhibitory effect of cucurbitacin B on breast cancer cells was assessed by MTT assay and colony formation assay. Methylation status of genomic DNA was determined by methylation-specific PCR. Gene and protein expression levels of all genes studied were analyzed by real-time RT-PCR and western blot. The results indicated that cucurbitacin B could inhibit cell growth in breast cancer cells. The oncogene promoters are usually hypomethylated in cancer cells. Upon cucurbitacin B treatment, upregulation of DNMT1 and obvious heavy methylation in the promoters of c-Myc, cyclin D1, and survivin, which consequently downregulated the expression of all these oncogenes, were observed. Hence, cucurbitacin B proved to be a potential cancer therapeutic agent, in part by inducing hypermethylation and silences the oncogenic activation.

The diterpene isocoronarin D (1) is a bioactive major constituent of labdane diterpene from the aerial parts of Curcuma comosa Roxb. (Zingiberaceae), the Thai medicinal plant. Microbial transformation of 1 was performed by the fungus Cunninghamella echinulata NRRL 1386 to yield three new metabolites, 3β-hydroxyisocoronarin D (2), 6α-hydroxyisocoronarin D (3) and 3β,7α-dihydroxyisocoronarin D (4). The structures of the new compounds were elucidated by spectroscopic techniques.

An efficient one-pot synthesis of novel andrographolide analogues is reported from a naturally occurring and abundant andrographolide isolated from aerial parts of Andrographis paniculata. Reactions in the one-pot proceed through a cascade epoxide ring opening by aniline derivatives/intramolecular ring closing and oxa-conjugate addition-elimination reactions. This methodology produces a new series of 17-amino-8-epi-isoandrographolide analogues in fair to excellent yields with high stereoselectivity using an economic and environmental procedure without base or catalyst at room temperature. Twenty-five analogues were obtained and cytotoxicity of all new analogues were evaluated against six cancer cell lines to search for a new lead compound based on andrographolide structure.