Design, synthesis and in vitro cytotoxicity of novel dinuclear platinum(II) complexes

Five dinuclear platinum(II) complexes with a novel chiral ligand, 2-(((1R,2R)-2-aminocyclohexylamino)methyl)phenol (HL), were designed, prepared and spectrally characterized. In vitro cytotoxicity of all the resulting platinum(II) compounds was evaluated against human HEPG-2, A549 and HCT-116 cell lines, respectively. Results indicated that all compounds showed positive biological activity. Particularly, compound D4 has lower IC₅₀ values than carboplatin toward HEPG-2 and A549, while compound D5 shows better activity than carboplatin against A549.     

New antitumor compounds from Carya cathayensis

A new lignan (7R,8S,8'R)-4,4',9-trihydroxy-7,9'-epoxy-8,8'-lignan, and three new phenolics, carayensin-A, carayensin-B, and carayensin-C, together with 13 known compounds were isolated from the shells of Carya cathayensis. Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry. All the compounds were evaluated for cytotoxicity against several human tumor types including human colorectal cancer cell lines (HCT-116, HT-29), human lung cancer cell line (A549), and human breast cancer cell line (MCF-7). The compounds 1, 5, 6, and 16 are considered to be potential as antitumor agents, which could significantly inhibit the cancer cell growth in a dose-dependent manner.     

ent-Pimarane Diterpenes from the Aerial Parts of Siegesbeckia pubescens

Five new ent-pimarane diterpenes ( 1 – 5 ) and five known analogs ( 6 – 10 ) were isolated from the aerial parts of Siegesbeckia pubescens. Their structures, including absolute configurations, were determined by comprehensive spectroscopic methods especially 1D and 2D NMR and quantum chemical electronic circular dichroism calculations. All the isolated compounds were evaluated for their cytotoxicity against human BT549, A549 and H157 cancer cell lines. Among them, compounds 1 and 2 showed mild cytotoxicity against lung cancer cell lines H157 with IC₅₀ values of 16.35±2.59 and 18.86±4.83 μM, respectively.     

Two new rotenoids from the roots of Millettia speciosa

Two new rotenoids, named millettiaosas A–B (1–2), together with four known compounds were isolated from the roots of Millettia speciosa. Their structures were elucidated on the basis of spectroscopic analysis including 1D and 2D NMR techniques and HRESIMS. Evaluation of the two new compounds for cytotoxicity against four human cancer cell lines (MCF-7, HCT-116, A549 and HepG-2) showed moderate activities (10 μM < IC₅₀ < 26 μM).     

Isolation,Cytotoxicity Evaluation and HPLC-Quantification of the Chemical Constituents from Prangos pabularia

Phytochemical analysis of the dichloromethane:methanol (1∶1) extract of root parts of Prangos pabularia led to the isolation of twelve cytotoxic constituents, viz., 6-hydroxycoumarin (1), 7-hydroxycoumarin (2), heraclenol-glycoside (3), xanthotoxol (4), heraclenol (5), oxypeucedanin hydrate (6), 8-((3,3-dimethyloxiran-2-yl)methyl)-7-methoxy-2H-chromen-2-one (7), oxypeucedanin hydrate monoacetate (8), xanthotoxin (9), 4-((2-hydroxy-3-methylbut-3-en-1-yl)oxy)-7H-furo[3,2-g]chromen-7-one (10), imperatorin (11) and osthol (12). The isolates were identified using spectral techniques in the light of literature. 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity screening of the isolated constituents was carried out against six human cancer cell lines including lung (A549 and NCI-H322), epidermoid carcinoma (A431), melanoma (A375), prostate (PC-3) and Colon (HCT-116) cell lines. Osthol (12) exhibited the highest cytotoxicity with IC₅₀ values of 3.2, 6.2, 10.9, 14.5, 24.8, and 30.2 µM against epidermoid carcinoma (A431), melanoma (A375), lung (NCI-H322), lung (A549), prostate (PC-3) and colon (HCT-116) cell lines respectively. Epidermoid carcinoma cell line A431 was sensitive to most of the compounds followed by lung (A549) cancer cell line. Finally a simple and reliable HPLC method was developed (RP-HPLC-DAD) and validated for the simultaneous quantification of these cytotoxic constituents in Prangos pabularia. The extract was analyzed using a reversed-phase Agilent ZORBAX eclipse plus column C₁₈ (4.6×250 mm, 5 µm) at 250 nm wavelength using a gradient water-methanol solvent system at a flow rate of 0.8 ml/min. The RP-HPLC method is validated in terms of recovery, linearity, accuracy and precision (intra and inter-day validation). This method, because of shorter analysis time, makes it valuable for the commercial quality control of Prangos pabularia extracts and its future pharmaceutical preparations.     

Design,synthesis and biological evaluation of six dinuclear platinum(II) complexes

Six dinuclear platinum(II) complexes with a chiral tetradentate ligand, (1R,1′R,2R,2′R)-N¹,N^1′-(1,4-phenylenebis(methylene))dicyclohexane-1,2-diamine, have been designed, synthesized and characterized. In vitro cytotoxicity evaluation of these metal complexes against human A549, HCT-116, MCF-7 and HepG-2 cell lines have been carried out. All compounds showed antitumor activity to HepG-2, HCT-116 and A549. Particularly, compounds A1 and A2 exhibited significant better activity than other four compounds and A2 even showed comparable cytotoxicity to cisplatin against HepG-2 cell line.     

Imidazopyridine linked triazoles as tubulin inhibitors,effectively triggering apoptosis in lung cancer cell line

A library of new imidazopyridine linked triazole hybrid conjugates (8a-r) were designed, synthesized and evaluated for their cytotoxicity against four cancer cell lines namely, human lung (A549), human prostate (DU-145), human colon (HCT-116) and breast (MDA-MB 231) cancer. These conjugates exhibited good to moderate activity against the tested human cancer cell lines. Two of the conjugates (8g and 8j) showed significant antitumor activity against human lung cancer cell line (A549) with IC₅₀ values of 0.51 µM and 0.63 µM respectively. Flow cytometry analysis revealed that these conjugates arrested the cell cycle at G₂/M phase in human lung cancer cell line (A549). Immune-histochemistry and tubulin polymerization assay suggest inhibition of tubulin. Hoechst staining, annexin V and DNA fragmentation by tunnel assay suggested that these compounds induce cell death by apoptosis. Overall, the current study demonstrates that the synthesis of imidazopyridine linked triazole conjugates as promising anticancer agents causing G₂/M arrest and apoptotic-inducing ability.     

Prenylated C6-C3 compounds with molecular diversity from the roots of Illicium oligandrum

Eleven prenylated C₆-C₃ compounds, illioliganpyranone A (1), illioliganfunone A-D (2-5), and illioliganone D-I (6-11), together with five known prenylated C₆-C₃ compounds (12-16), were isolated from roots of Illicium oligandrum. The structures of 1-11 were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, and CD experiments. Possible biosynthetic pathways to compounds 1-16 derived from a common precursor of 5-allylbenzene-1,2,4-triol were postulated. All compounds were evaluated for cytotoxic activities against five human cancer cell lines (HCT-8, Bel-7402, BGC-823, A549 and A2780). Compound 15 exhibited significant cytotoxicity against HCT-8, BGC-823, A549, and A2780 cell lines with IC₅₀ values of 0.30-2.57 μM. Compound 16 showed moderate selective cytotoxicity against sensitive A2780 cells with IC₅₀ value of 1.38 μM.     

Aminoadamantanes containing monoterpene-derived fragments as potent tyrosyl-DNA phosphodiesterase 1 inhibitors

The ability of a number of nitrogen-containing compounds that simultaneously carry the adamantane and monoterpene moieties to inhibit Tdp1, an important enzyme of the DNA repair system, is studied. Inhibition of this enzyme has the potential to overcome chemotherapeutic resistance of some tumor types. Compound (+)-3c synthesized from 1-aminoadamantane and (+)-myrtenal, and compound 4a produced from 2-aminoadamantane and citronellal were found to be most potent as they inhibited Tdp1 with IC₅₀ values of 6 and 3.5 µM, respectively. These compounds proved to have low cytotoxicity in colon HCT-116 and lung A-549 human tumor cell lines (CC₅₀ > 50 µM). It was demonstrated that compound 4a at 10 µM enhanced cytotoxicity of topotecan, a topoisomerase 1 poison in clinical use, against HCT-116 more than fivefold and to a lesser extent of 1.5 increase in potency for A-549.     

Cytotoxic and Anti‐inflammatory Sesquiterpenes from Ainsliaea henryi

Three new sesquiterpenoids, 4α‐hydroxyeudesm‐11(13)‐en‐12‐yl 3‐methylbutanoate ( 1 ), diaspanolide E ( 2 ), and (13α)‐germacra‐1(10),4‐dien‐12,8α‐olid‐15‐oic acid ( 3 ), along with eight known sesquiterpenoids ( 4 – 11 ), were isolated from the aerial parts of Ainsliaea henryi. The chemical structures of compounds 1 – 3 were elucidated by spectroscopic analysis (1D‐, 2D‐NMR, MS and HR/MS). All isolates were evaluated for their inhibitory activities against nitric oxide (NO) production in lipopolysaccharide‐induced RAW264.7 macrophage cells. Compound 10 exhibited significantly inhibition against NO release with an IC₅₀ value of 6.54 ± 0.16 μm . Also, all isolated compounds were tested for cytotoxicity against three human tumor cell lines A549, MGC803, and HCT116, among which compound 5 significantly inhibited the proliferation of MGC803 cell lines with an IC₅₀ value of 2.2 ± 0.2 μm .     

Chemical Constituents of the Vietnamese Marine Sponge Gelliodes sp. and Their Cytotoxic Activities

A new decenoic acid derivative, gelliodesinic acid, and a naturally new alkaloid, together with three known furanoterpenoids and two known indole alkaloids, were isolated from the MeOH extract of the marine sponge Gelliodes sp. collected in Vietnam. The chemical structures of the isolated compounds were determined by analyses of 1D‐ and 2D‐NMR and MS data and by comparisons of the data with those reported in the literature. The cytotoxicity assay against HeLa, MCF‐7, and A549 cancer cell lines revealed that the three known furanoterpenes exhibited cytotoxic activities with IC₅₀ values ranging from 23.6 to 75.5 μM against the three cell lines, and that 1H‐indole‐3‐carboxylic acid showed cytotoxicity with an IC₅₀ value of 89.2 μM against A549 cancer cell lines.     

Chemical Constituents of Primulina eburnea (Gesneriaceae) and Their Cytotoxic Activities

Two new ursane-type triterpenes, eburnealactones A and B ( 1 and 2 ), one new flavonoid, eburneatin A ( 6 ), and one new phenylethanoid glycoside, chiritoside D ( 7 ), along with 9 known compounds ( 3–5 , 8–13 ) were isolated from the whole plant of Primulina eburnea. Their structures were elucidated by comprehensive spectroscopic data analysis (IR, UV, NMR, and HR-ESI-MS). All the compounds were evaluated for their cytotoxic activities. Compound 1 showed significant cytotoxic activities against MKN-45 cell lines and 5637 cell lines with the IC₅₀ values of 9.57 μM and 8.30 μM, respectively. Compound 1 exhibited moderate cytotoxic activities against A549 and PATU8988T cell lines with the IC₅₀ values of 30.70 μM and 38.22 μM, respectively. Compound 6 exhibited moderate cytotoxic activities against MKN-45, HCT116, PATU8988T, 5637 and A-673 cell lines with the IC₅₀ values of 19.69 μM, 16.44 μM, 18.07 μM, 11.51 μM and 18.15 μM, respectively. Compound 5 showed moderate cytotoxic activities against A549 cell lines with the IC₅₀ values of 24.06 μM.     

Lactarane sesquiterpenoids from Lactarius subvellereus and their cytotoxicity

Subvellerolactones B (1), D (2), and E (3), structurally unusual lactarane sesquiterpenoids, were isolated from the fruiting bodies of Lactarius subvellereus together with four known lactarane sesquiterpenes (4–7). The chemical structures and stereochemistries of compounds 1–3 were determined on the basis of spectroscopic analyses, including 1D and 2D NMR experiments and a convenient Mosher ester procedure. Subvellerolactone B (1) exhibited cytotoxicity against the A549, SK-MEL-2, and HCT-15 cell lines with IC₅₀ values of 26.5, 18.3, and 14.2 μM, respectively, and subvellerolactones D (2) and E (3) showed cytotoxicity against the A549 and HCT-15 cell lines (IC₅₀ (2): 25.1 and 17.8 μM, and IC₅₀ (3): 19.6 and 28.7 μM, respectively).     

Triterpenoid Saponins with Potential Cytotoxic Activities from the Root Bark of Ilex rotunda Thunb.

A new 19‐oxo‐18,19‐seco‐ursane‐type triterpeonoid saponin, laevigin E ( 8 ), together with 17 known compounds ( 1 – 7 and 9 – 18 ) were isolated from the root bark of Ilex rotunda Thunb . Their structures were determined by various spectroscopic analysis. Among them, compounds 6 , 9 , 11 , and 18 were isolated from this species for the first time, while compounds 10 and 12 were firstly isolated from the family Aquifoliaceae. Biological activity assay showed that all triterpenoids exhibit moderate cytotoxic activities against MCF7, A549, HeLa and LN229 cell lines. The four triterpenoid saponins ( 3 , 4 , 6 , and 8 ) exhibit slightly better activities compared to the four triterpenoid sapogenins ( 1 , 2 , 5 , and 7 ). Compound 8 showed the best cytotoxicity against A549, HeLa and LN229 cell lines with IC₅₀ of 17.83, 22.58 and 30.98 μm , respectively.     

Synthesis and characterisation of celastrol derivatives as potential anticancer agents

In the present study, three series of novel celastrol derivatives were designed and synthesised by modifying the carboxylic acid at the 20th position with amino acid, amine, and triazole derivatives. All the synthesised compounds were screened for their anticancer activities using MTT assay against AGS, MGC-803, SGC-7901, HCT-116, A549, HeLa, BEL-7402, and HepG-2 cell lines. Most of the synthesised compounds exhibited potent antiproliferative effects. The most promising compound 3-Hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic amide, N-(R)-methyl-3-(1H-indol-2-yl)propanoate (11) showed considerable high anticancer activity against AGS cell lines, with an IC₅₀ value of 0.44?μM, and considerably higher activities against HCT-116, BEL-7402, and HepG-2 cell lines, with IC₅₀ values of 0.78, 0.63, and 0.76?μM, respectively. The results of apoptosis tests and molecular docking study of compound 11 binding to Caspase-3 revealed that its mechanism of action with antiproliferative was possibly involved in inducing apoptosis by inducing the activation of caspase-3.     

Anticancer evaluation and molecular modeling of multi-targeted kinase inhibitors based pyrido[2,3-d]pyrimidine scaffold

An efficient synthesis of substituted pyrido[2,3-d]pyrimidines was carried out and evaluated for in vitro anticancer activity against five cancer cell lines, namely hepatic cancer (HepG-2), prostate cancer (PC-3), colon cancer (HCT-116), breast cancer (MCF-7), and lung cancer (A-549) cell lines. Regarding HepG-2, PC-3, HCT-116 cancer cell lines, 7-(4-chlorophenyl)-2-(3-methyl-5-oxo-2,3-dihydro-1H-pyrazol-1-yl)-5-(p-tolyl)- pyrido[2,3-d]pyrimidin-4(3H)-one (5a) exhibited strong, more potent anticancer (IC₅₀: 0.3, 6.6 and 7?µM) relative to the standard doxorubicin (IC₅₀: 0.6, 6.8 and 12.8?µM), respectively. Kinase inhibitory assessment of 5a showed promising inhibitory activity against three kinases namely PDGFR β, EGFR, and CDK4/cyclin D1 at two concentrations 50 and 100?µM in single measurements. Further, a molecular docking study for compound 5a was performed to verify the binding mode towards the EGFR and CDK4/cyclin D1 kinases.     

Benzylisoquinoline alkaloids from the tubers of Corydalis ternata and their cytotoxicity

Chemical investigation of the tubers of Corydalis ternata resulted in the isolation and characterization of four new benzylisoquinoline alkaloids, epi-coryximine (1) and coryternatines A–C (2–4), along with 10 known alkaloids (5–14). Their structures were established on the basis of extensive spectroscopic data analyses and comparison with spectroscopic data reported. In addition, the cytotoxicities of the alkaloids (1–14) were evaluated by determining their inhibitory effects on several human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) using the SRB assay. Compound 8 showed significant cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines (IC₅₀ = 8.34, 5.14, 7.87, and 2.86 μM, respectively). The four new compounds (1–4) exhibited selective cytotoxicity against the HCT-15 cell line.     

Alkaloids from Cephalotaxus lanceolata and Their Cytotoxicities

A phytochemical investigation of the branches and leaves of Cephalotaxus lanceolata resulted in the isolation of three new cephalotaxus alkaloids, cephalancetines A, B, and D ( 1, 2 , and 4 , resp.), together with ten known alkaloids, 3 and 5 – 13 . The structures of the alkaloids were elucidated on the basis of spectroscopic analyses, including 1D‐ and 2D‐NMR, and HR‐ESI‐MS, and single‐crystal X‐ray diffraction. All isolated compounds were tested for their cytotoxicities against four human tumor cell lines, A549, HCT116, SK‐BR‐3, and HepG2. Compounds 12 and 13 showed remarkable activities against A549, HCT116, and HepG2 cell lines.     

Synthesis and cytotoxicity of novel imidazo[4,5-d]azepine compounds derived from marine natural product ceratamine A

A series of novel imidazo[4,5-d]azepine compounds derived from marine natural product ceratamine A were designed and synthesized in 7 steps. Most compounds exhibited comparable cytotoxicity against five human cancer cell lines (HCT-116, HepG2, BGC-823, A549 and A2780) to natural product ceratamine A. Compound 1k, bearing methoxy group at C-14, C-15 and C-16, showed the best in vitro cytotoxicity, which was better than ceratamine A. The structure and activity relationships study showed that the benzyloxymethyl group on N-3 played an important role on the cytotoxicity.     

Four New Diterpenoid Alkaloids from the Roots of Aconitum carmichaelii

Aconitum carmichaelii Debeaux is a widely used traditional Chinese medicine and an important source of clinical drugs, of which the parent and lateral roots are known as ‘Chuanwu’ and ‘Fuzi’, respectively. Four new C₁₉‐diterpenoid alkaloids, carmichasines A – D ( 1 – 4 ), were isolated from the roots of Aconitum carmichaelii, together with twelve known compounds ( 5 – 16 ). Their structures were elucidated via spectroscopic analyses, including HR‐ESI‐MS, IR, and NMR. Carmichasine A ( 1 ) is the first natural C₁₉‐diterpenoid alkaloid possessing a cyano group. Most of the diterpenoid alkaloids isolated were C₁₉‐category, which might provide further clues for understanding the chemotaxonomic significance of this plant. The cytotoxicity of the new compounds was also investigated against several human cancer cell lines, including MCF‐7, HCT116, A549, and 786‐0, and none of them showed considerable cytotoxic activity.