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As diiron subsite models of [FeFe]‐hydrogenases for catalytic proton reduction to hydrogen (H2), a new series of the phosphine‐substituted diiron ethanedithiolate complexes Fe2(μ‐edt)(CO)6‐nLn (n = 1, 2) were prepared from the variable substitutions of all‐CO precursor Fe2(μ‐edt)(CO)6 (A) and tertiary phosphines (L1‐L4) under different reaction conditions. While the Me3NO‐assisted substitutions of A and one equiv. ligands L1‐L4 [L = Ph2P(CH2NHBut), Ph2P(CH2CH2NH2), Ph2P(NHBut), and Ph2P(C6H4Me‐p)] produced the monosubstituted complexes Fe2(μ‐edt)(CO)5L (1–4) in good yields, the refluxing xylene solution of A and two equiv. ligand L1 prepared complex Fe2(μ‐edt)(CO)5{κ1‐Ph2P(CH2NHBut)} (1) in low yield. Meanwhile, the UV‐irradiated toluene solution of A and two equiv. ligand L3 resulted in the rare formation of the disubstituted complex Fe2(μ‐edt)(CO)4{κ1, κ1‐(Ph2PNHBut)2} (5) in low yield, whereas the Me3NO‐assisted substitution of A and two equiv. ligand L4 afforded the disubstituted complex Fe2(μ‐edt)(CO)4{κ1, κ1‐(Ph2PC6H4Me‐p)2} (6) in good yield. All the model complexes 1–6 have been characterized by elemental analysis, FT‐IR, NMR spectroscopy, and particularly for 1, 3, 5 by X‐ray crystallography. Further, the protonations of complexes 1–4 are studied and compared with excess acetic acid (HOAc) and trifluoroacetic acid (TFA) by using FT‐IR and NMR techniques. Additionally, the electrochemical and electrocatalytic properties of model complexes 1–6 are investigated and compared by cyclic voltammetry (CV), suggesting that they are electrocatalytically active for proton reduction to H2 in the presence of HOAc. [ABSTRACT FROM AUTHOR]

As the biomimetic models of [FeFe]-hydrogenase active sites, two new di- and mononuclear iron complexes with chelating PNP ligands (PNP = (Ph2P)2NR) have been prepared and structurally determined by single-crystal X-ray diffraction analysis. Treatment of precursor Fe2(μ-edt)(CO)6 (A, edt = SCH2CH2S) with diphosphine (Ph2P)2N(CHMe2) in the presence of Me3NO·2H2O in MeCN produced a dinuclear iron complex Fe(μ-edt)(CO)4{κ2-(Ph2P)2N(CHMe2)} (1), whereas the similar reaction of Fe2(μ-odt)(CO)6 (B, odt = SCH2OCH2S) with (Ph2P)2N(CH2)3Me afforded a mononuclear iron complex Fe(κ2-odt)(CO)2{κ2-(Ph2P)2N(CH2)3Me} (2). The crystal structure of 1 contains a butterfly [Fe2S2] cluster, whereas that of 2 exhibits a square bipyramidal geometry of Fe atom. [ABSTRACT FROM AUTHOR]

In this paper, five diiron propane-1,3-dithiolate complexes containing substituted phosphine ligands were prepared and structurally characterized. Treatment of [Fe2(CO)6(μ-SCH2CH2CH2S)] (1) with a monophosphine ligand methyl diphenylphosphinite, ethyl diphenylphosphinite, 4-(dimethylamino)phenyldiphenylphosphine, tris(2-methoxyphenyl)phosphine, or tris(4-chlorophenyl)phosphine in the presence of Me3NO·2H2O as the decarbonylating agent gave the corresponding phosphine-substituted analogues [Fe2(CO)5(L)(μ-SCH2CH2CH2S)] [L = Ph2POCH3, 2; Ph2POCH2CH3, 3; Ph2P(4-C6H4 NMe2), 4; P(2-C6H4OCH3)3, 5; P(4-C6H4Cl)3, 6] in 73–93% yields. Complexes 2–6 have been characterized by elemental analysis, spectroscopy, and X-ray crystallography. Additionally, electrochemical studies have shown that 2–6 can catalyze the reduction of protons to H2 in the presence of HOAc. [ABSTRACT FROM AUTHOR]

In order to discover new anticancer drug leads, a series of novel alkylamino pyrimidine derivatives were designed and synthesized based on our previous work via a ring-opening strategy. Biological evaluation with four human cancer cell lines (MDA-MB-231, A549, HepG2, and MCF-7) showed that most of these compounds possessed moderate to potent antiproliferative activities. The most promising compound 7w displayed a three-fold improvement compared with commercial anticancer drug fluorouracil in inhibiting HepG2 cell proliferation with IC 50 value of 10.37 μM. Moreover, flow-activated cell sorting analysis suggested that compound 7w mainly arrested HepG2 cells in G 2 /M stage. Hence, it could serve as a promising lead for the design of novel anticancer small-molecule drugs. [ABSTRACT FROM AUTHOR]

Based on our previous work, a series of novel 3-alkylsulfanyl-4-amino-1,2,4-triazole derivatives were designed, synthesized and evaluated for their antiproliferative activities. The results indicated that some compounds possessed significant antiproliferative activities against four cancer cell lines, HepG2, HCT116, PC-3, and Hela. Particularly, the most promising compound 8d displayed 184-, 18-, and 17-fold improvement compared to fluorouracil in inhibiting HCT116, Hela and PC-3 cell proliferation with IC 50 values of 0.37, 2.94, and 31.31 μM, respectively. Most interestingly, the compound did not affect the normal human embryonic kidney cells, HEK-293. Moreover, mechanistic investigation showed that the representative compound 8d induced apoptosis and blocked cell cycle in G 2 /M phase in Hela cells in a dose-dependent manner. These findings suggest that compound 8d may have potential to be developed as a promising lead for the design of novel anticancer small-molecule drugs. [ABSTRACT FROM AUTHOR]

Two new diiron dithiolate complexes [(μ-SCH2)2CHCO2R][Fe2(CO)6] (R = -C10H7-β,1; -C6H4Me-m,2) bearing thiolate-bridged-carboxy functionality, which are closely related to the active site of [FeFe]-hydrogenase, have been synthesized by esterification reaction of parent complex [(μ-SCH2)2CHCO2H][Fe2(CO)6] (A) and C10H7OH-β or HOC6H4Me-min the presence of 4-dimethylaminopyridine (DMAP) and dicyclohexylcarbodiimide (DCC). These new complexes were characterized by elemental analysis, FTIR, as well as1H (13C) NMR spectroscopy, and particularly for1by X-ray crystallography. Furthermore, the thiolate-bridged-carboxy functionality (namely, the ester group) resides in an equatorial position in the chair conformation of the six-membered rings (FeS2C3) in crystal structure of1. [ABSTRACT FROM PUBLISHER]

In order to develop an attractive generation of bulky oxadithiolate-bridged [FeFe]‑hydrogenase mimics with chelating diphosphines, two new series of asymmetrically diphosphine-substituted diiron model complexes [Fe 2 (μ -R 2 odt)(CO) 4 (κ 2 -diphosphine)] (3 – 5) with bulky Ph 2 odt bridge and their reference counterparts (6 – 8) with common odt bridge were obtained from the Me 3 NO-assisted substitutions of diiron hexacarbonyl precursors [Fe 2 (μ -R 2 odt)(CO) 6 ] (R 2 odt = (SCHR) 2 O, R = Ph (1) and H (2)) with different diphosphines such as (Ph 2 P) 2 NBn (labelled PNBnP, Bn = benzyl), (Ph 2 PCH 2) 2 NBn (PCNBnCP), and (Ph 2 PCH 2) 2 CH 2 (DPPP)), respectively. All the as-prepared complexes have been characterized by elemental analysis, IR plus NMR spectroscopies, and particularly by X-ray crystallography for 3 – 8. It is interesting to note that complexes 3 and 6 chelating by small bite-angle PNBnP diphosphine have the favorable dibasal isomer whereas analogues 4 , 5 and 7 , 8 chelating by flexible backbone PCNBnCP or DPPP ligands possess the main apical-basal isomer in solution or in the solid state. Further, the electrochemical properties of two pairs of representative complexes 3 , 6 and 5 , 8 are explored and compared by cyclic voltammetry (CV) in the absence and presence of trifluoroacetic acid (CF 3 CO 2 H) as proton source, indicating that the complete protonations of 3 , 6 and 5 , 8 with higher concentration of CF 3 CO 2 H lead to two new catalytic waves for the electrocatalytic proton reduction to hydrogen (H 2). A new generation of bulky oxadithiolate-bridged [FeFe]‑hydrogenase mimics 3 – 5 and counterparts 6 – 8 were prepared. Ligand effects (i.e., R 2 odt bridges and chelating diphosphines) on their structures and electrocatalytic H 2 evolution are explored. [Display omitted] • Bulky R 2 odt-bridged [FeFe]‑hydrogenase mimics 1 – 8 were prepared and characterized. • Structural and electrochemical comparisons of 3 – 8 with chelating diphosphines are performed. • Small bite-angle diphosphine (PNP) in 3 and 6 occupy favorable dibasal manner. • Flexible backbone disphosphines (PCNCP or DPPP) in 4 , 5 , 7 , 8 show main apical-basal modes. • Protonations of 3 , 6 and 5 , 8 with higher [CF 3 CO 2 H] lead to the electrocatalytic H 2 evolution. [ABSTRACT FROM AUTHOR]

To investigate the influence of bridgehead-C functionality in diiron dithiolate complexes on the molecular structure and electrocatalytic properties of [FeFe]-hydrogenase models, three new bridgehead-C-functionalized model complexes1–3have been synthesized and structurally characterized. Treatments of parent complex [(μ-SCH2)2CHCO2H][Fe2(CO)6] (A) with the esterification agentso-MeC6H4OH,p-ClC6H4OH, orp-HOC6H4CHO in the presence of 4-dimethylaminopyridine and dicyclohexylcarbodiimide in CH2Cl2at room temperature resulted in formation of [(μ-SCH2)2CHCO2R][Fe2(CO)6] (R = o-MeC6H4–,1;p-ClC6H4–,2;p-OHCC6H4–,3) in 53–55% yields. The new complexes1–3were characterized by elemental analysis, IR and NMR spectroscopy, and especially determined by X-ray crystallography. The electrochemical properties of1–3and the electrocatalytic H2evolution catalyzed by1have been investigated by cyclic voltammetry, where1is a catalyst for HOAc proton reduction to H2under electrochemical conditions. [ABSTRACT FROM PUBLISHER]

Two chalcone compounds, namely (E)-1-phenyl-3-[(2,4,6-trimethylphenyl)]prop-2-en-1-one (1) and (E)-1-phenyl-3-[(4-trifluoromethylphenyl)]prop-2-en-1-one (2), have been synthesized and structurally characterized by elemental analysis,1H NMR spectrum, and single-crystal X-ray diffraction analysis. The chalcone molecules in (1) and (2) have the common skeleton of 1,3-diaryl-2-propen-1-one and adopt an (E)-configuration about the C = C double bonds. In addition, X-ray analysis reveals that theπ···πstacking interactions are well observed in the crystal structure of (1) and (2). [ABSTRACT FROM PUBLISHER]

Highlights: [•] Polycarboxylate (PC) additive for CWS was synthesized and characterized. [•] PC additive is a comblike polymer with COOH and CONH2 groups. [•] CWS based on bituminous coal with PC additive displayed better properties. [•] Simultaneously using of PC and aliphatic additives enhanced the CWS performance. [•] PC additive exhibited improved properties because of its steric hindrance effect. [Copyright &y& Elsevier]

Abstract: Four new carboxy-functionalized diiron propanedithiolate complexes 1–4 have been successfully synthesized and fully characterized. The all-carboxyl complexes [(μ-SCH2)2CHCO2CH2CH2Cl][Fe2(CO)6] (1) and [(μ-SCH2)2CHCO2C6H4I-p][Fe2(CO)6] (2) were prepared by the condensation reaction of the known complex [(μ-SCH2)2CHCO2H][Fe2(CO)6] (A) with ClCH2CH2OH and p-IC6H4OH in the presence of 4-dimethylaminopyridine (DMAP) and dicyclohexylcarbodiimide (DCC) in yields of 46% and 66%, whereas the phosphine-substituted complexes [(μ-SCH2)2CHCO2CH2CH2Cl][Fe2(CO)5PPh3] (3) and [(μ-SCH2)2CHCO2CH2CH2Cl][Fe2(CO)4(PPh3)2] (4) were further synthesized through the carbonyl substitution reaction of 1 with PPh3 using the decarbonylating agent Me3NO·2H2O in yields of 44% and 41%. The new complexes 1–4 were characterized by combustion analysis, IR and 1H, 13C and 31P NMR spectroscopic techniques. The molecular structures of 1–4 were unequivocally determined by single crystal X-ray diffraction analysis, in which the carboxy-functionalized substituent attached to the bridgehead-C atom resides in an equatorial position of the six-membered rings in the solid state. [Copyright &y& Elsevier]

Abstract: A series of 3,4-disubstituted-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazoles and some novel 5,6-dihydro-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles bearing 3,4,5-trimethoxyphenyl moiety were synthesized and screened for their anticancer activity. The preliminary bioassay results indicated that compounds 14 and 16 showed much stronger cytotoxicity than Doxorubicin against HepG2 cell lines with IC50 values of 0.58 and 3.17μM, respectively. Meanwhile compound 16 also exhibited a broad spectrum of antitumor activity against MCF-7 and MKN45 with IC50 values of 10.92 and 13.79μM, respectively. [Copyright &y& Elsevier]

Lung cancer is one of the most common cancers and the leading cause of death in humans worldwide. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases and is often diagnosed at a late stage. Among patients with NSCLC, 50% die within 1 year after diagnosis. Even with clinical intervention, the 5-year survival rate is only approximately 20%. Therefore, the development of an advanced therapeutic strategy or novel agent is urgently required for treating NSCLC. Berberine exerts therapeutic activity toward NSCLC; therefore, its activity as an antitumor agent needs to be explored further. In this study, three terpenylated-bromide derivatives of berberrubine were synthesized and their anti-NSCLC activities were evaluated. Each derivative had higher anti-NSCLCs activity than berberrubine and berberine. Among them, 9-O-gernylberberrubine bromide (B4) and 9-O-farnesylberberrubine bromide (B5) showed greater growth inhibition, cell-cycle regulation, in vitro tumorigenesis suppression, and tumor migration reduction. In addition, some degree of apoptosis and autophagic flux blocking was noted in the cells under B4 and B5 treatments. Our study demonstrates that the berberrubine derivatives, B4 and B5, exhibit impressive anti-NSCLC activities and have potential for use as chemotherapeutic agents against NSCLC. [ABSTRACT FROM AUTHOR]

In an effort to better probe the structure–function relationship on the biological [Fe4S4] cluster of [FeFe]‐hydrogenases, a new library of tertiary phosphine‐supported diiron dithiolate complexes [Fe2(μ‐adtNR)(CO)5{P(C6H4X)3}] (1–3) with various substituents (X = F vs. H vs. Me), wherein adtNR is denoted as abbreviation for the (SCH2)2N(C6H4C2H4OC(O)CH2C6H4Me) unit, is prepared as the active site mimics of [FeFe]‐hydrogenases. Notably, the substituent influences of tertiary phosphines on the structures and electrochemical behaviors of 1–3 are studied by spectroscopic and crystallographic techniques as well as cyclic voltammetry. For example, the electronic effect of tertiary phosphines [P(C6H4X)3] is responsible for the electron density around diiron center and the key Fe–Fe as well as Fe–P lengths in 1–3 as revealed by IR spectroscopy and crystallographic analysis. Further, complexes 1–3 show the electrochemical activity for proton reduction into molecular hydrogen (H2) using acetic acid (AcOH) as a proton source. Noticeably, F‐substituent‐containing diiron model complex 1 exhibits greater turnover frequency (i.e., turnover frequency value) and similar overpotential for electrocatalytic H2 evolution relative to H‐ or Me‐substituent‐bearing diiron homologs 2 or 3. [ABSTRACT FROM AUTHOR]

Five monophosphine‐substituted diiron propane‐1,2‐dithiolate complexes as the active site models of [FeFe]‐hydrogenases have been synthesized and characterized. Reactions of complex [Fe2(CO)6{μ‐SCH2CH(CH3)S}] (1) with a monophosphine ligand tris(4‐methylphenyl)phosphine, diphenyl‐2‐pyridylphosphine, tris(4‐chlorophenyl)phosphine, triphenylphosphine, or tris(4‐fluorophenyl)phosphine in the presence of the oxidative agent Me3NO·2H2O gave the monophosphine‐substituted diiron complexes [Fe2(CO)5(L){μ‐SCH2CH(CH3)S}] [L = P(4‐C6H4CH3)3, 2; Ph2P(2‐C5H4N), 3; P(4‐C6H4Cl)3, 4; PPh3, 5; P(4‐C6H4F)3, 6] in 81%–94% yields. Complexes 2–6 have been characterized by elemental analysis, spectroscopy, and X‐ray crystallography. In addition, electrochemical studies revealed that these complexes can catalyze the reduction of protons to H2 in the presence of HOAc. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Based on our previous work, 29 novel triazolylthioacetamides possessing 3,4,5-trimethoxylphenyl groups were synthesized. • 8f and 8j showed potent antiproliferative activities against Hela with IC 50 values of 0.04 and 0.05 μM, respectively. • 8b exhibited potent antitubulin activity with IC 50 values of 5.9 μM, which was proximate to CA-4 (IC 50 = 4.2 μM). Abstract Based on our previous research, three series of new triazolylthioacetamides possessing 3,4,5-trimethoxyphenyl moiety were synthesized, and evaluated for antiproliferative activities and inhibition of tubulin polymerization. The most promising compounds 8b and 8j demonstrated more significant antiproliferative activities against MCF-7, HeLa, and HT-29 cell lines than our lead compound 6. Moreover, analogues 8f , 8j , and 8o manifested more potent antiproliferative activities against HeLa cell line with IC 50 values of 0.04, 0.05 and 0.16 μM, respectively, representing 100-, 82-, and 25-fold improvements of the activity compared to compound 6. Furthermore, the representative compound, 8j , was found to induce significant cell cycle arrest at the G 2 /M phase in HeLa cell lines via a concentration-dependent manner. Meanwhile, compound 8b exhibited the most potent tubulin polymerization inhibitory activity with an IC 50 value of 5.9 μM, which was almost as active as that of CA-4 (IC 50 = 4.2 μM). Additionally, molecular docking analysis suggested that 8b formed stable interactions in the colchicine-binding site of tubulin. [ABSTRACT FROM AUTHOR]

A novel diiron S-(−)-1-phenylethylazadithiolate complex, Fe 2 [( μ -SCH 2 ) 2 NCH(CH 3 )Ph](CO) 6 ( 1 ), has been prepared by the condensation of Fe 2 ( μ -SH) 2 (CO) 6 , CH 2 O and S-(−)-1-phenylethylamine. Furthermore, the reaction of complex 1 and phosphine ligands (PPh 3 , P(C 6 H 4 -4-F) 3 , dppe) in the presence of the decarbonylation agent Me 3 NO·2H 2 O resulted in the formation of the phosphine-substituted diiron S-(−)-1-phenylethylazadithiolate complexes Fe 2 [( μ -SCH 2 ) 2 NCH(CH 3 )Ph](CO) 5 (PPh 3 ) ( 2 ), Fe 2 [( μ -SCH 2 ) 2 NCH(CH 3 )Ph](CO) 5 [P(C 6 H 4 -4-F) 3 ] ( 3 ) and {Fe 2 [( μ -SCH 2 ) 2 NCH(CH 3 )Ph](CO) 5 } 2 (Ph 2 PCH 2 CH 2 PPh 2 ) ( 4 ). Complexes 1 – 4 have been fully characterized by elemental analysis, FTIR and NMR ( 1 H, 13 C, 31 P) spectroscopies, and for 1 , 2 and 4 by X-ray crystallography. Moreover, complexes 1 and 2 were found to be catalysts for hydrogen production in the presence of acid under electrochemical conditions. According to the electrochemical observations, a possible catalytic mechanism for complexes 1 and 2 was proposed. [ABSTRACT FROM AUTHOR]

As the active site models of [FeFe]-hydrogenases, two new aminophosphine-monosubstituted diiron dithiolate compelxes with the general formulae Fe 2 ( μ -pdt)(CO) 5 {PPh 2 NH(C 6 H 4 R- p )} (pdt = SCH 2 CH 2 CH 2 S; R = Br ( 1 ), Me ( 2 )), were prepared by the oxidative decarbonylation of parent Fe 2 ( μ -pdt)(CO) 6 ( A ) with monophosphines Ph 2 PNH(C 6 H 4 Br- p ) or Ph 2 PNH(C 6 H 4 Me- p ) in the presence of decarbonylating agent Me 3 NO·2H 2 O in MeCN. Interestingly, the ambient temperature treatment of A and aminodiphosphine Ph 2 PN(C 6 H 4 Me- p )PPh 2 resulted in the formation of the major chelated complex Fe 2 ( μ -pdt)(CO) 4 { κ 2 -Ph 2 PN(C 6 H 4 Me- p )PPh 2 } ( 3 ) concomitant with the minor complex 2 . All the complexes 1 - 3 have been well characterized by elemental analysis, FTIR, NMR ( 1 H, 31 P) spectroscopies, and X-ray crystallography. Additionally, the electrochemical and electrocatalytic properties of complexes 1 - 3 are studied using cyclic voltammetry, where the ratios of the catalytic current ( i cat ) to the reductive peak current ( i p ) for similar complexes 1 , 2 , and parent A at 10 mM HOAc exhibit a ranking of 2 ≈ 1 > A . [ABSTRACT FROM AUTHOR]

Three novel diiron azadithiolate complexes Fe 2 [( μ -SCH 2 ) 2 NCH 2 CH 2 CH(CH 3 ) 2 ](CO) 6 ( 1 ), Fe 2 [( μ -SCH 2 ) 2 NCH(CH 2 CH 3 ) 2 ](CO) 6 ( 2 ) and Fe 2 [( μ -SCH 2 ) 2 NCH 2 CH 2 CH 2 SCH 3 ](CO) 6 ( 3 ) have been synthesized by treatment of Fe 2 ( μ -SCH 2 OH) 2 (CO) 6 with primary amines RNH 2 (R = CH 2 CH 2 CH(CH 3 ) 2 , CH(CH 2 CH 3 ) 2 , CH 2 CH 2 CH 2 SCH 3 ). Meanwhile, reaction of Fe 2 ( μ -SCH 2 OH) 2 (CO) 6 and diphosphine ligand Ph 2 PCH 2 PPh 2 (dppm), followed by the addition of amines NH 2 CH 2 CH 2 CH(CH 3 ) 2 and NH 2 CH(CH 2 CH 3 ) 2 resulted in the formation of the target phosphine-substituted diiron azadithiolate complexes Fe 2 [( μ -SCH 2 ) 2 NCH 2 CH 2 CH(CH 3 ) 2 ](CO) 5 (dppm) ( 4 ) and Fe 2 [( μ -SCH 2 ) 2 NCH(CH 2 CH 3 ) 2 ](CO) 5 (dppm) ( 5 ). Complexes 1 – 5 have been fully characterized by elemental analysis, FTIR, and NMR ( 1 H, 13 C, 31 P) spectroscopies, and particularly for 1 – 3 by X-ray crystallography. In addition, complexes 1 – 5 were found to be catalysts for hydrogen production under electrochemical conditions. [ABSTRACT FROM AUTHOR]

Based on our previous work, a series of novel 2-amino-7,8-dihydropteridin-6(5 H )-one derivatives were designed and synthesized via a ring-closing strategy. Biological evaluation with four human cancer cell lines (BT549, T47D, MDA-MB-468, and MDA-MB-231) showed that most of these compounds possessed moderate to potent antiproliferative activities. The most promising compound 8-benzyl-2-(phenethylamino)-7,8-dihydropteridin-6(5 H )-one ( 6q ) possessing IC 50 values of 7.75, 6.37, and 10.73 μM against MDA-MB-468, T47D, and BT549, respectively, which were 49, 11, and 8 folds more active than the positive control fluorouracil. Moreover, fluorescence-activated cell sorting analysis revealed that compound 6q displayed a significant effect on G1 cell-cycle arrest in a concentration-dependent manner in T47D cells. The initial structure–activity relationship studies indicated that linker-length of amine chain in C-2 position of pyrimidine ring played a crucial role in modulating the antitumor activity, which could be of help in the rational design of dihydropteridin-6(5 H )-ones as novel anticancer drugs. [ABSTRACT FROM AUTHOR]

Three diiron and tetrairon azadithiolate complexes as models for the active site of [FeFe] hydrogenase were prepared. Reaction of complex Fe2(SCH2OH)2(CO)6 and NH2CH2CH2CH2OCH3 resulted in the diiron azadithiolate hexcarbonyl complex Fe2[(SCH2)2- NCH2CH2CH2OCH3](CO)6 (1) in moderate yield. Furthermore, treatment of complex 1 with mono phosphine ligand PPh3 and diphosphine ligand PH2PCH2CH2PPH2 in the presence of decarbonylation reagent Me3NO·2H2O yielded the phosphine-substituted azadithiolate complexes Fe2[(SCH2)2NCH2CH2CH2OCH3]CO)5(PPh3) (2) and {Fe2[(SCH2)2NCH2CH2CH2OCH3](CO)5}2(PH2PCH2CH2PPH2) (3) respectively. The new complexes 1-3 were fully characterized by elemental analysis, IR, ¹H, 13C, 31P NMR spectroscopy and X-ray crystallography. It is worthy to note that the crystallographic studies show the unusual difference of the methoxypropanyl substituent on the N atom of complexes 1 and 2, largely because of the affection of phosphine ligand PPh3. In addition, complex 1 was found to be a catalyst for H2 production under electrochemical condition. [ABSTRACT FROM AUTHOR]

Thirty-two novel 3-alkylsulfanyl-1,2,4-triazole derivatives, designed as cis -restricted combretastatin A-4 analogues, were synthesized and evaluated for their antiproliferative activities. The results indicated that analogue 20 showed more potent antiproliferative activities against PC-3 cell lines than positive control CA-4. Particularly, the most promising compound 25 displayed 5-fold improvement compared to CA-4 in inhibiting HCT116 cell proliferation with IC 50 values of 1.15 μM. Further flow-activated cell sorting analysis revealed that compound 20 displayed a significant effect on G 2 /M cell-cycle arrest in a dose-dependent manner in PC-3 cells. From this study, analogues 20 and 25 were the most potent anti-cancer agents in this structural class, and were considered lead compounds for further development as anti-cancer drugs. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of new 6-arylamino-[1,2,4]triazolo[4,3- a ]pyridine were synthesized following our prior work. • 8 l significantly broadened antitumor spectrum when compared with the lead compound 6. • 8 l exhibited potent and broad-spectrum antiproliferative activity on tested cell lines. • 8 l dose-dependently caused G 2 /M phase arrest and induced cell apoptosis in HeLa cells. Based on our previous work, a series of novel 6-arylamino-[1,2,4]triazolo[4,3- a ]pyridine derivatives were synthesized, and evaluated for antiproliferative activities. SAR studies revealed that inserting an amino linkage between 6‑aryl group and [1,2,4]triazolo[4,3- a ]pyridine core led to a much broader antitumor spectrum, and the most promising compound 8 l exerted potent and broad-spectrum antiproliferative activity toward HeLa, HCT116, MCF-7, and A549 cell lines, with IC 50 values in the micromolar range of 5.98–12.58 μM, which were more active than the positive control 5-FU. The mechanism investigation illustrated that 8 l dose-dependently caused cell cycle arrest at the G 2 /M phase, and induced cell apoptosis in HeLa cells. Consequently, these findings suggest the 6-arylamino-[1,2,4]triazolo[4,3- a ]pyridines afford significant potential for the discovery of a new highly efficient anticancer agents. [ABSTRACT FROM AUTHOR]

[Display omitted] • Based on our previous work, a series of triazolylthioacetones were synthesized. • IIc showed comparable potency with CA-4 on HT-29, HCT116, and HepG2 cells. • IIc exhibited the most potent antiproliferative activity on HT-29 with an IC 50 of 0.62 μM. • IIc displayed a significant inhibition of tubulin polymerization with an IC 50 value of 12.7 μM. Based on our previous work, a series of novel triazolylthioacetones incorporating pyridine, pyrazine, and 3,4,5-trimethoxybenzyl fragment were synthesized, and evaluated for antiproliferative activities and interactions with tubulin. Some analogues exhibited moderate to excellent potency, with the most promising compound IIc possessing IC 50 values of 0.62, 1.46, and 3.65 μM against HT-29, HCT116, and HepG2 tumor cells, respectively, which were comparable with the positive control CA-4. Mechanistical studies revealed that IIc concentration-dependently caused cell cycle arrest at the G 2 /M phase in HCT116 tumor cells, and displayed a significant inhibition of tubulin polymerization with an IC 50 value of 12.7 μM. Moreover, molecular docking analysis suggested that IIc could occupy the colchicine-binding site in a similar way with typical tubulin polymerization inhibitors. These results highlighted the 4-amino-triazolylthioacetone scaffold as potential tubulin polymerization inhibitors for development of highly efficient anticancer agents. [ABSTRACT FROM AUTHOR]

[Display omitted] In order to discover new anticancer agents, 25 novel 2,4-diamino-5-methyleneaminopyrimidine derivatives were designed and synthesized based on our previous work via a ring-opening strategy. Among them, compared with 5-FU, compound 7i exhibited 4.9-, 2.9-, 2.1-, and 3.0-fold improvement in inhibiting HCT116, HT-29, MCF-7, and HeLa cells proliferation with IC 50 values of 4.93, 5.57, 8.84, and 14.16 μM, respectively. Moreover, further mechanistic studies indicated that compound 7i could concentration-dependently induce cell cycle arrest and apoptosis in HCT116 cells. These findings revealed that 2,4-diamino-5-methyleneaminopyrimidine scaffold has potential for further investigation to explore novel anticancer agents. [ABSTRACT FROM AUTHOR]

[Display omitted] • Thirty new 5-amino-1 H -1,2,4-triazoles as novel CA-4 analogues were synthesized. • IIa and I IIm showed significant antiproliferative activities on a panel of tumor cell lines. • IIa exhibited potent tubulin polymerization inhibitory activity with an IC 50 value of 9.4 μM. Based on our previous research, thirty new 5-amino-1 H -1,2,4-triazoles possessing 3,4,5-trimethoxyphenyl moiety were synthesized, and evaluated for antiproliferative activities. Among them, compounds IIa , IIIh , and IIIm demonstrated significant antiproliferative activities against a panel of tumor cell lines, and the promising compound IIIm dose-dependently caused G2/M phase arrest in HeLa cells. Furthermore, analogue IIa exhibited the most potent tubulin polymerization inhibitory activity with an IC 50 value of 9.4 μM, and molecular modeling studies revealed that IIa formed stable interactions in the colchicine-binding site of tubulin, suggesting that 5-amino-1 H -1,2,4-triazole scaffold has potential for further investigation to develop novel tubulin polymerization inhibitors with anticancer activity. [ABSTRACT FROM AUTHOR]

• A novel class of 8-cyclopentyl-7,8-dihydropteridin-6(5H)-ones were synthesized. • 6k possessed potent antiproliferative activity against HCT-116, HeLa, and HT-29. • 6k induced HeLa cells arrested in G2/M phase via a concentration-dependent manner. Based on our previous work, a novel class of 8-cyclopentyl-7,8-dihydropteridin-6(5H)-one derivatives were synthesized and evaluated as antiproliferative agents. Structure-activity relationship analysis revealed that the greatest activities were achieved with a 4-(4-methylpiperazin-1-yl)aniline group at C-2 position of dihydropteridin-6(5H)-one core, and the most promising compound 6k demonstrated comparable antiproliferative activity with Palbociclib and more potent than our parent derivative 4 toward four cell lines including HCT-116, HeLa, HT-29, and MDA-MB-231 with IC 50 values of 3.29, 6.75, 7.56, and 10.30 μM, respectively. Moreover, the mechanism studies revealed that compound 6k could induce cell cycle arrest at G2/M phase via a concentration-dependent manner. In general, these preliminary observations suggested that these compounds could serve as promising scaffolds for further modification to develop novel and highly potent cancer therapy agents. [ABSTRACT FROM AUTHOR]

On the basis of our previous work, twenty-nine novel [1,2,4]triazolo[4,3-a]pyridines possessing 3,4,5-trimethoxylphenyl groups were designed, synthesized, and evaluated as tubulin polymerization inhibitors. The bioassay results revealed that some of the compounds displayed excellent antiproliferative efficacies in the nanomolar range against HeLa cells, and the most promising derivative 7i demonstrated almost comparable activity to that of the reference CA-4 and sixty-two fold more potent than the parent compound 6 with an IC 50 value of 12 nM. Importantly, 7i exhibited high selectivity over the normal human embryonic kidney HEK-293 cells (IC 50 > 100 μM). Further mechanism studies revealed that 7i significantly arrested cell cycle at G2/M phase, induced apoptosis with a dose-dependent manner, and disrupted microtubule networks. Additionally, the most active compound 7i effectively inhibited tubulin polymerization with a value similar to that of CA-4 (3.4 and 4.2 μM, respectively). Furthermore, molecular docking analysis suggested that 7i well occupied the colchicine binding pocket of tubulin. The present study highlights that compound 7i is a novel potential tubulin polymerization inhibitor and deserves further investigation for the treatment of cancers. Image 1 • 29 novel 3,6-diaryl-[1,2,4]triazolo[4,3-a]pyridines were synthesized. • 7i displayed an IC 50 of 0.012 nM on HeLa and high selectivity over normal human cell HEK-293. • 7i possessed potent antitubulin activity with a value similar to CA-4 (3.4 and 4.2 μM, respectively). • 7i caused cell cycle arrest and apoptosis and disrupted microtubule networks. [ABSTRACT FROM AUTHOR]

• A series of novel 3,4,5-trimethoxylbenzamide substituted benzofurans were prepared. • 6g possessed potent antiproliferative activity on MDA-MB-231, HCT-116, and HT-29. • 6g induced HeLa cells arrest in G2/M phase, and inhibited tubulin polymerization. A new series of derivatives characterized by the presence of the 3,4,5-trimethoxylbenzamide substituted benzofurans were synthesized and evaluated for antiproliferative activity against four cancer cell lines and one normal human cell line. Among them, derivative 6g with greatest cytotoxicity significantly inhibited the growth of MDA-MB-231, HCT-116, HT-29 and HeLa cell lines with IC 50 values of 3.01, 5.20, 9.13, and 11.09 μM, respectively. Importantly, 6g possessed excellent selectivity over non-tumoral cell lines HEK-293 (IC 50 > 30 μM). Moreover, mechanistic studies revealed that 6g induced HeLa cells arrested in G2/M phase in a concentration-dependent manner, and inhibited polymerization of tubulin via a consistent way with CA-4. In general, these observations suggest that 6g is a promising anti-cancer lead and is worth further investigation to generate potential antitumor agents. [ABSTRACT FROM AUTHOR]

Twenty-six novel pyrazolo[3,4- b ]pyridine-bridged analogues of combretastatin A-4 possessing 3,4,5-trimethoxylphenyl groups, were synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. Preliminary biological evaluation demonstrated that some of the target compounds displayed significant antiproliferative effect against four different cell lines including MCF-7, MDA-MB-231, HeLa and Kyse150. The most active analogue 6n was found to induce HeLa cells arrest in the G2/M phase in a dose-dependent manner. Molecular modeling studies indicated that derivative 6n most likely occupies the colchicine site of tubulin. The initial results suggest that the 3,4,5-trimethoxyphenyl substituted pyrazolo[3,4- b ]pyridine could serve as a promising scaffold for development of potent tubulin inhibitors as anticancer agents. [ABSTRACT FROM AUTHOR]

• A series of novel indole-based oxalamide and aminoacetamide derivatives were synthesized. • 8g exhibited significant antiproliferative effect against PC-3, HeLa and HCT-116 cell lines. • Immunocytochemistry revealed loss of intact microtubule structure in cells treated with 8g. A series of novel indole-based oxalamide and aminoacetamide derivatives were designed, synthesized, and evaluated for antiproliferative activities. Preliminary results revealed that compound 8g exhibited significant antiproliferative effect against PC-3, HeLa and HCT-116 cell lines. Flow cytometric analysis of the cell cycle demonstrated the compound 8g induced the cell cycle arrest at G2/M phase in HeLa cell lines. Immunocytochemistry revealed loss of intact microtubule structure in cells treated with 8g and inhibition of tubulin polymerization. Additionally, molecular docking analysis suggested that 8g formed stable interactions in the colchicine-binding site of tubulin. These preliminary results demonstrated that a new class of novel indole-based oxalamide and aminoacetamide derivatives described in the investigation could be developed as potential scaffolds to new anticancer agents. [ABSTRACT FROM AUTHOR]

A new series of diiron aminophosphine complexes 1 – 5 with the adtNPh bridge and reference analogue 7 have been obtained, aiming to better observe and compare the influence of pendant amines of phosphine ligands on the structures and electrocatalytic properties of diiron model complexes related to [FeFe]-hydrogenases in this work. • New diiron aminophosphine complexes 1 – 5 and reference analogues 6 , 7 were synthesized. • All the complexes are characterized by elemental analysis, various spectroscopies, and X-ray crystallography for 1 , 2 , 4 , 7. • Structural and electrochemical comparisons of 1 – 5 and 7 are studied. Me 3 NO-assisted substitution reactions of precursor Fe 2 (μ -adtNPh)(CO) 6 (A , adtNPh = SCH 2 N(Ph)CH 2 S) and aminodiphosphines (Ph 2 P) 2 NR with different N -aryl substituents (R) resulted in the unexpected formation of five new diiron aminophosphine complexes Fe 2 (μ -adtNPh)(CO) 5 { κ1 -Ph 2 P(NHR)} (R = C 6 H 5 (1), C 6 H 4 Me- p (2), C 6 H 4 OMe- p (3), C 6 H 4 CO 2 Me- p (4), and C 6 H 4 Cl- p (5)) with adtNPh bridge, which may be regarded as the active site models of [FeFe]-hydrogenases. In order to further observe the influence of the pendant amines of phosphine ligands on the formation, structures, and electrochemical properties of model complexes 1 – 5 obtained above, two reference analogues Fe 2 (μ -adtNPh)(CO) 5 (κ1 -dppm) (6 , dppm = (Ph 2 P) 2 CH 2) and Fe 2 (μ -adtNPh)(CO) 5 { κ1 -Ph 2 P(CH 2 Ph)} (7) were prepared from the similar treatment of A with the dppm or Ph 2 P(CH 2 Ph) ligands, respectively. Meanwhile, these new complexes 1 – 5 and 7 have been characterized by elemental analysis, FT-IR and NMR (1H, 31P) spectroscopies, and particularly for 1 , 2 , 4 , 7 by X-ray crystallography, in which the P atoms of the Ph 2 P(NHR) ligands in 1 , 2 , 4 reside in an apical position whereas that of the Ph 2 P(CH 2 Ph) ligand in 7 occupies at a basal site in the solid state. In addition, the electrochemical and electrocatalytic behaviors of 1 – 5 and 7 are investigated and compared in the absence and presence of acetic acid (HOAc) as proton source using cyclic voltammetry (CV), indicating they are all found to be active eletrocatalysts for proton reduction to hydrogen (H 2). [ABSTRACT FROM AUTHOR]