Eight Indole Alkaloids from the Roots of Maerua siamensis and Their Nitric Oxide Inhibitory Effects

Maerua siamensis (Capparaceae) roots are used for treating pain and inflammation in traditional Thai medicine. Eight new indole alkaloids, named maeruanitriles A and B, maeroximes A–C, and maeruabisindoles A–C, were isolated from them. Spectroscopic methods and computational analysis were applied to determine the structure of the isolated compounds. Maeroximes A–C possesses an unusual O-methyloxime moiety. The bisindole alkaloid maeruabisindoles A and B possess a rare azete ring, whereas maeruabisindole C is the first indolo[3,2-b]carbazole derivative found in this plant family. Five compounds [maeruanitriles A and B, maeroxime C, maeruabisindoles B, and C] displayed anti-inflammatory activity by inhibiting nitric oxide (NO) production in the lipopolysaccharide-induced RAW 264.7 cells. Maeruabisindole B was the most active inhibitor of NO production, with an IC₅₀ of 31.1 ± 1.8 μM compared to indomethacin (IC₅₀ = 150.0 ± 16.0 μM) as the positive control.     

Lignanamides and Sesquiterpenoids from Stems of Mitrephora thorelii

The first phytochemical investigation on stems of Mitrephora thorelii led to the isolation of three new lignanamides, thoreliamides A–C ( 1 – 3 ), and a new sesquiterpenoid, thorelinin ( 4 ), together with ten known compounds. The structures of the new compounds were established on the basis of extensive spectroscopic analyses. Thoreliamide C is the first trimer derived from cinnamic acid amide units.     

Design and Synthesis of New Thiophene/Thieno[2,3-d]pyrimidines along with Their Cytotoxic Biological Evaluation as Tyrosine Kinase Inhibitors in Addition to Their Apoptotic and Autophagic Induction

This work describes the synthesis and anticancer activity against kinase enzymes of newly designed thiophene and thieno[2,3-d]pyrimidine derivatives, along with their potential to activate autophagic and apoptotic cell death in cancer cells. The designed compounds were scanned for their affinity for kinases. The results were promising with affinity ranges from 46.7% to 13.3%. Molecular docking studies were performed, and the compounds were then screened for their antiproliferative effects. Interestingly, compounds 8 and 5 resulted in higher cytotoxic effects than the reference standard against MCF-7 and HepG-2. The compounds were evaluated for their induction of apoptosis and/or necrosis on HT-29 and HepG-2. Three compounds induced significant early apoptosis compared to untreated control HT-29 cells, and four derivatives were more significant compared to untreated HepG-2 cells. We further investigated the effect of four compounds on the autophagy process within HT-29, HepG-2, and MCF-7 cells with flow cytometry. Similar to the apoptosis results, compound 5 showed the highest autophagic induction among all compounds. The potential inhibitory activity of the synthesized compounds on kinases was assessed. Screened compounds showed inhibition activity ranging from 41.4% to 83.5%. Compounds recorded significant inhibition were further investigated for their specific FLT3 kinase inhibitory activity. Noticeably, Compound 5 exhibited the highest inhibitory activity against FLT3.     

Powerful Antioxidants and Cytotoxic Activities of the Methanol Extracts from Eight Soybean Cultivars

In the present study, the chemical composition and total phenolic (TPC) and total flavonoid contents (TFC) of eight soybean cultivars (Giza 21, Giza 22, Giza 35, Giza 111, Giza 82, Giza 83, Crawford, and Holliday) were estimated. Moreover, antioxidant activity and in vitro cytotoxic activities against HepG-2 and MCF-7 were evaluated. Giza 21, Giza 111, and Crawford cultivars recorded higher than 40% crude protein. The analysis revealed that TPC values in seed extracts ranged from 10.5 mg GAE/g extract in Giza 35 to 6.4 mg GAE/g extract in Giza 22. TFC varied from 1.20 mg QE/g extract in Giza 111 to 0.55 mg QE/g extract in Crawford. Giza 35 exhibited the highest content of genistein and daidzein and the highest free radical scavenging activity (61.833%). The results of the MTT assay demonstrated that the soybean methanolic extracts inhibited the proliferation of HepG-2 and MCF-7 cells in a dose-dependent manner. Giza 35 exhibited the highest cytotoxic activity. In conclusion, Giza 35 cultivar recorded the highest TPC and TFC values and antioxidant and cytotoxic activities. Therefore, this cultivar can be used as a source for the production of pharmaceutical and medicinal products rather than as a nutritional source of protein.     

New Flavonoid Derivatives from Melodorum fruticosum and Their α-Glucosidase Inhibitory and Cytotoxic Activities

Three new flavonoid derivatives, melodorones A–C (1–3), together with four known compounds, tectochrysin (4), chrysin (5), onysilin (6), and pinocembrin (7), were isolated from the stem bark of Melodorum fruticosum. Their structures were determined on the basis of extensive spectroscopic methods, including NMR and HRESIMS, and by comparison with the literature. Compounds 1–7 were evaluated for their in vitro α-glucosidase inhibition and cytotoxicity against KB, Hep G2, and MCF7 cell lines. Among them, compound 1 exhibited the best activity against α-glucosidase and was superior to the positive control with an IC₅₀ value of 2.59 μM. On the other hand, compound 1 showed moderate cytotoxicity toward KB, Hep G2, and MCF7 cell lines with the IC₅₀ values of 23.5, 19.8, and 23.7 μM, respectively. These findings provided new evidence that the stem bark of M. fruticosum is a source of bioactive flavonoid derivatives that are highly valuable for medicinal development.     

Ent-Abietane Diterpenoids from Euphorbia fischeriana and Their Cytotoxic Activities

The roots of Euphorbia fischeriana have been used as a traditional Chinese medicine for the treatment of tuberculosis and ringworm. In the current study, diterpenoids from the ethyl acetate extract of the roots E. fischeriana and their cytotoxic effects against five cancer lines were investigated. Two new ent-abietane diterpenoids, euphonoids H and I (1–2), as well as their two analogues (3–4) were first isolated from this source. The structures of the two new compounds were elucidated on the basis of spectroscopic data and quantum chemical calculation. Their absolute configurations were assigned via ECD spectrum calculation. The isolated compounds were evaluated for their antiproliferative activities against five cancer cell lines. Compounds 1 and 2 exhibited significant inhibitory effects against human prostate cancers C4-2B and C4-2B/ENZR cell lines with IC₅₀ values ranging from 4.16 ± 0.42 to 5.74 ± 0.45 μM.     

Chemical Constituents from Acanthopanax senticosus and Their Cytotoxic Activities

Chemistry of Natural Compounds - A new lignan, named 1,6-bis-(3-methoxy-4-hydroxyphenyl)hexane-1,6-dione (1), together with seven known compounds (2–8) were isolated from the EtOAc-soluble...     

Structural Insight and Development of EGFR Tyrosine Kinase Inhibitors

Lung cancer has a high prevalence, with a growing number of new cases and mortality every year. Furthermore, the survival rate of patients with non-small-cell lung carcinoma (NSCLC) is still quite low in the majority of cases. Despite the use of conventional therapy such as tyrosine kinase inhibitor for Epidermal Growth Factor Receptor (EGFR), which is highly expressed in most NSCLC cases, there was still no substantial improvement in patient survival. This is due to the drug’s ineffectiveness and high rate of resistance among individuals with mutant EGFR. Therefore, the development of new inhibitors is urgently needed. Understanding the EGFR structure, including its kinase domain and other parts of the protein, and its activation mechanism can accelerate the discovery of novel compounds targeting this protein. This study described the structure of the extracellular, transmembrane, and intracellular domains of EGFR. This was carried out along with identifying the binding pose of commercially available inhibitors in the ATP-binding and allosteric sites, thereby clarifying the research gaps that can be filled. The binding mechanism of inhibitors that have been used clinically was also explained, thereby aiding the structure-based development of new drugs.     

Labdane Diterpenoids from the Roots of Amomum maximum and Their Cytotoxic Evaluation

A rare labdane diterpene γ‐lactam, 1 , and two new labdane diterpenoids, 2 and 3 , along with two known diterpenes, 4 and 5 , were isolated from the roots of Amomum maximum. Their structures were established on the basis of spectroscopic data. All of the isolates were evaluated for their cytotoxic activities, and compound 3 was found to exhibit an inhibitory activity against MG‐63 cell lines with an IC₅₀ value of 3.3±0.8 μg/ml.     

Two New Flavanols from Glycosmis pentaphylla and Their Cytotoxic Activities

Two new flavanols, (8S,9R)‐9,10‐dihydro‐5,9‐dihydroxy‐8‐(3,4,5‐trimethoxyphenyl)‐2H,8H‐benzo[1,2‐b:3,4‐b′]dipyran‐2‐one ( 1 ) and (2S,3R)‐3,4‐dihydro‐3,5‐dihydroxy‐2‐(3,4,5‐trimethoxyphenyl)‐2H,8H‐benzo[1,2‐b:3,4‐b′]dipyran‐8‐one ( 2 ), were isolated from the stems of Glycosmis pentaphylla. The structures of these compounds were determined by extensive spectroscopic (UV, IR, HR‐ESI‐MS, 1D‐ and 2D‐NMR) analyses. The cytotoxic activities of these compounds were evaluated using the MTT method. The results showed that compounds 1 and 2 exhibited considerable cytotoxic activities against HL‐60 and A549 cell lines.     

Diterpenoids from Aerial Parts of Clerodendranthus spicatus and Their Cytotoxic Activity

A chemical investigation of AcOEt‐soluble portion of the 95% EtOH extract of the aerial parts of Clerodendranthus spicatus led to the isolation and characterization of a new diterpenoid, named clerospicasin J ( 1 ). Structure elucidation of 1 was achieved by spectroscopic analyses, including 2D‐NMR. The diterpenoid 1 exhibited significant inhibitory activity on the proliferation of the SKOV3 cell lines. Moreover, the cytotoxicity of 1 against SKOV3 cells was related to apoptotis as confirmed by DAPI (=2‐(4‐amidinophenyl)‐1H‐indole‐6‐carboxamidine) nuclear staining and flow cytometry.     

Secondary Metabolites from the Fungus Monascus purpureus and Evaluation of Their Cytotoxic Activity

Investigation of the 95% EtOH extract of red yeast rice fermented with the fungus Monascus purpureus BCRC 31615 has led to the isolation and structure elucidation of four new compounds, including one new azaphilone analog, monascuspurpurone ( 1 ), a new isocoumarin, monaschromone ( 2 ), a new furan‐3‐one derivative, 2‐dodecyl‐5‐(2‐methoxyethyl)‐2‐methylfuran‐3(2H)‐one ( 3 ), and a new alkaloid, methyl 4‐[(E)‐2‐acetyl‐4‐oxoundec‐1‐enyl]‐6‐propylnicotinate ( 4 ), together with seven known compounds. The structures of all isolates were elucidated on the basis of extensive spectroscopic analyses and comparison with literature data. Compounds 1 – 4 were tested for their cytotoxicity against the MCF‐7, NCI‐H460, and SF‐268 cell lines using the MTT (=3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) assay. Among them, compounds 1 and 4 were found to have moderate cytotoxic effects against these three cell lines in vitro.     

Secondary Metabolites from the Stem Bark of Litsea akoensis and Their Cytotoxic Activity

Six new butanolides, litseadioxanins A and B ( 1 and 2 , resp.) bearing a 1,2‐dioxane moiety, litseatrinolides A and B ( 3 and 4 , resp.), and litseakolides D₁ and D₂ ( 5 and 6 , resp.), were isolated from the stem bark of Litsea akoensis, together with six known compounds. The structures of the new compounds were characterized by in‐depth NMR‐spectroscopic and mass‐spectrometric analyses. Butanolides 1 – 4 , and a mixture of 6 and litsenolide E₂, and litsenolide B₁ were tested against human tumor cells, including MCF‐7 (human breast adenocarcinoma), NCI‐H460 (non‐small‐cell lung cancer), and SF‐268 (glioblastoma) cell lines. Among the tested compounds, litsenolide B₁ exhibited marginal cytotoxic activity against MCF‐7, NCI‐H460, and SF‐268 cell lines in vitro.     

Cucurbitane Triterpenoids from the Fruit Pulp of Momordica charantia and Their Cytotoxic Activity

Two new cucurbitane‐type triterpenes, 25‐methoxycucurbita‐5,23(E)‐diene‐3β,19‐diol ( 1 ) and 7β‐ethoxy‐3β‐hydroxy‐25‐methoxycucurbita‐5,23(E)‐dien‐19‐al ( 2 ), together with three known cucurbitane‐type triterpenes, 3β,7β,25‐trihydroxycucurbita‐5,23(E)‐dien‐19‐al ( 3 ), (23E)‐3β‐hydroxy‐7β,25‐dimethoxycucurbita‐5,23‐dien‐19‐al ( 4 ), and 3β‐hydroxy‐25‐methoxycucurbita‐6,23(E)‐dien‐19,5β‐olide ( 5 ), were isolated from the fruit pulp of Momordica charantia. The structures of two new compounds were elucidated on the basis of 1D and 2D NMR, MS, IR, optical rotation. Among these isolates, compounds 1 , 2 , and 5 showed slight cytotoxic activity against the SK‐Hep 1 cell line with IC₅₀ values of 33.1, 24.3, and 38.7 μM, respectively.     

Guaiane Sesquiterpenoids Isolated from the Fruits of Torilis japonica and Their Cytotoxic Activity

Two new guaiane sesquiterpenoids, 11‐(acetyloxy)‐1,8‐dihydroxyguai‐4‐en‐3‐one ( 5 ) and (1α,6β)‐1,6‐dihydroxytorilin ( 6 ), were isolated from the fruits of Torilis japonica (Umbelliferae), along with four known sesquiterpenes, torilin ( 1 ), torilolone ( 2 ), (1β)‐1‐hydroxytorilin ( 3 ), and (1α)‐1‐hydroxytorilin ( 4 ). During the phytochemical investigation, daucosterol, friedelin, and epifriedelanol were also isolated from the plant for the first time. The structures of the new sesquiterpenoids 5 and 6 were determined by comprehensive analyses of MS and NMR spectroscopic data. These isolates were evaluated against human breast cancer cells (MCF‐7) and Lewis lung carcinoma (LLC) cells. Compounds 1, 3 , and 4 exhibited cytotoxic activity against the LLC cells with IC₅₀ values of 31.3, 32.5, and 34.0 μg/ml, respectively. However, no significant cytotoxicity was found against the MCF‐7 cells for any of the compounds tested.     

Indole Alkaloids from Strychnos Species and Their Antiplasmodial and Cytotoxic Activites

Indole alkaloids from the African Strychnos species, their antiplasmodial and cytotoxic action, and structure -activity relationships are discussed in the review     

Four New Pregnane Steroids from Aglaia abbreviata and Their Cytotoxic Activities

Four new pregnane steroids, aglaiasterols A–D ( 1 – 4 ), have been isolated from the EtOH extract of stems of Aglaia abbreviata. They were identified as (3α,5α,17Z)‐3‐hydroxypregn‐17‐en‐16‐one ( 1 ), (3β,5α,17E)‐3‐hydroxypregn‐17‐en‐16‐one ( 2 ), (3β,5α,17Z)‐3‐hydroxypregn‐17‐en‐16‐one ( 3 ), and (3α,5α,20S*)‐3‐hydroxy‐16‐oxopregnan‐20‐yl acetate ( 4 ) on the basis of spectroscopic methods, including 1D‐ and 2D‐NMR techniques. Compounds 1 – 4 were evaluated for their cytotoxic activities against K562 (human leukemia), MCF‐7 (human breast cancer), and KB (human oral epithelium cancer) cells, and drug‐resistant cells of K562/A02, MCF‐7/ADM, and KB/VCR. These isolates showed weak to moderate inhibitory effects on the growth of the tested cell lines.     

New Terpenoids from Potentilla freyniana Bornm. and Their Cytotoxic Activities

Two new A-ring contracted triterpenoids, madengaisu A and madengaisu B, and one undescribed ent-kaurane diterpenoid, madengaisu C, along with 20 known compounds were isolated from the roots of Potentilla freyniana Bornm. The structures were elucidated using extensive spectroscopic techniques, including 1D and 2D-NMR, HR-ESI-MS, ECD spectra, IR, and UV analysis. Moreover, all isolated constituents were evaluated for their anti-proliferative activity against RA-FLS cells and cytotoxic activities against the human cancer cell lines Hep-G2, HCT-116, BGC-823, and MCF-7. Ursolic acid and pomolic acid displayed moderate inhibitory activity in RA-FLS cells with IC₅₀ values of 24.63 ± 1.96 and 25.12 ± 1.97 μM, respectively. Hyptadienic acid and 2α,3β-dihydroxyolean-12-en-28-oic acid 28-O-β-d-glucopyranoside exhibited good cytotoxicity against Hep-G2 cells with IC₅₀ values of 25.16 ± 2.55 and 17.66 ± 1.82 μM, respectively. In addition, 2α,3β-dihydroxyolean-13(18)-en-28-oic acid and alphitolic acid were observed to inhibit HCT-116 cells (13.25 ± 1.65 and 21.62 ± 0.33 μM, respectively), while madengaisu B and 2α,3β-dihydroxyolean-13(18)-en-28-oic acid showed cytotoxic activities against BGC-823 cells with IC₅₀ values of 24.76 ± 0.94 and 26.83 ± 2.52 μM, respectively, which demonstrated that triterpenes from P. freyniana may serve as therapeutic agents for RA and cancer treatment.