Synthesis of selectively deuterated and tritiated lupane derivatives with cytotoxic activity

The aim of this work was to synthesize deuterated and tritiated analogues of highly oxidized lupane derivatives known from our group. We selected compounds that previously showed very high cytotoxic activity on multiple cancer cell lines in order to further investigate the mechanism of their action. From starting material (compounds 1–4), we obtained benzyl platanate (5) and its reaction with deuteromethyltriphenylphosphonium iodide gave deuterated compound 6. Following benzyl deprotection gave free acid 7 and oxidation with SeO₂ gave 30-oxo-[29-²H₂]lup-20(29)-en-28-oic acid (8), which is one of the most active compounds synthesized in our group to date (IC₅₀ 6 μmol/L on CEM cell line). The alkylation of benzyl 2-hydroxy-3-oxolupa-1,20(29)-dien-28-oate (9) with methyliodide or deuteromethyliodide followed by a series of deprotection and hydrogenation steps gave compounds 10–14, where 2β-[31-²H₃]methoxy-3-oxolupan-20(29)-en-28-oic acid (13) is especially interesting, it showed lower activity on CEM cell line (IC₅₀ 10 μmol/L) however, it was very active against Ph1—positive human leukemia BV-173 (IC₅₀ 0.91 μmol/L) and against human myelogenous leukemia K562 (IC₅₀ 0.52 μmol/L). Selectively labelled [3α-²H] and [3α-³H] methyl 3β-acetoxy-21,22-dioxolup-18-en-28-oates 24, 25 were prepared in three steps by reduction of corresponding 3-oxo derivatives and they showed moderate activity on CEM cell line (IC₅₀ 10 μmol/L). In total, 11 labelled compounds (6–8, 11, 14, 18, 19, 21, 22, 24 and 25) have not been reported before.     

Novel 2H-pyrazolo[4,3-c]hexahydropyridine derivatives: Synthesis, crystal structure, fluorescence properties and cytotoxicity evaluation against human breast cancer cells

A series of novel 2H-pyrazolo[4,3-c]hexahydropyridine derivatives (II) have been designed and synthesized. The target compounds have been identified by elemental analysis and spectral (¹H NMR, IR, and MS) data and the absolute configuration of compound (II ₁ ) was confirmed by single crystal X-ray diffraction. The cytotoxicity of the target compounds have been evaluated in vitro against two human breast cancer cell lines MCF-7 and MDA-MB-231 by MTT assay. Most compounds exhibited good inhibition, and compounds II ₂₁ (IC₅₀ = 4.7 μM for MCF-7 and IC₅₀ = 9.3 μM for MDA-MB-231), II ₃₃ (IC₅₀ = 2.4 μM for MCF-7 and IC₅₀ = 4.2 μM for MDA-MB-231) and II ₄₀ (IC₅₀ = 3.3 μM for MCF-7 and IC₅₀ =8.6 μM for MDA-MB-231) displayed better inhibitory activity than 5-fluorouracil (IC₅₀ = 4.8 μM for MCF-7 and IC₅₀ = 9.6 μM for MDA-MB-231, respectively). Flow cytometric analysis and DNA fragmentation suggest that II ₃₃ is cytotoxic and able to induce the apoptosis of MCF-7 cells. The fluorescence properties of compounds II ₁ , II ₆ , II ₁₁ , II ₁₆ , II ₂₃ , II ₂₈ , and II ₃₅ were also studied and compound II ₂₈ afforded the highest photoluminescence quantum yield (38%).     

Synthesis, spectroscopic characterization and structure-activity relationship of some phosphoramidothioate pesticides

In this work, some phosphoramidothioates (PATs) with the general formula of (CH₃O)₂P(S)X and (CH₃O)(CH₃S)P(O)X, where, X = NH₂ (1 & 6), NH(CH₃) (2 & 7), N(CH₃)₂ (3 & 8), N(Et)₂ (4 & 9), (CH₃CH₂O)₂P(S)NH(CH₃) (5) and (CH₃CH₂O)(CH₃CH₂S)P(O)NH(CH₃) (10), were synthesized and characterized by ³¹P, ³¹P{¹H}, ¹³C and ¹H NMR spectroscopy. The ability of the compounds to inhibit AChE was predicted by PASS software (version 1.193). They were also experimentally evaluated by a modified Ellman??s assay. The structure-activity relationship (SAR) between IC50 and some physico-chemical properties such as lipophilicity (logP), electronic and steric effects of the compounds was studied. The logP values were experimentally determined by the shake-flask (gas chromatography) method. Inhibitory potency for the compounds 1?C10 was 1 (3.38 mM) > 2 (3.97 mM) > 3 (4.75 mM) > 4 (6.00 mM) > 5 (5.51 mM) > 6 (0.07 mM) > 7 (0.23 mM) > 8 (0.39 mM) > and 9 (0.55 mM) > 10 (0.51 mM), respectively. IC₅₀ and logP parameters of the P=O moiety were more than the P=S moiety in PAT analogues.     

Synthesis and structure of Bis(tetraphenylantimony) 1,2-diphenylethanedione dioximate toluene solvate Ph4SbONC(Ph)C(Ph)ONSbPh4 · 2PhCH3 and tetraphenylantimony 2-hydroxy-1,2-diphenylethanone oximate Ph4SbONC(Ph)CH(Ph)OH

Bis(tetraphenylantimony) 1,2-diphenylethanedione dioximate toluene solvate Ph₄SbONC(Ph)C(Ph)NOSbPh₄ · 2 PhCH₃ (I) and tetraphenylantimony 2-hydroxy-1,2-diphenyl(ethanone oximate Ph₄SbONC(Ph)CH(Ph)OH (II) have been synthesized by the reaction of pentaphenylantimony with 1,2-diphenylethane dioxime and 2-hydroxy-1,2-diphenylethanone oxime in toluene. A molecule of compound I is centrosymmetric with an inversion center at the midpoint of the C-C bond in the ethane moiety. A crystal of compound II contains two types of crystallographically independent molecules A and B. Antimony atoms in compounds I and II have a distorted tetragonal bipyramidal surrounding: equatorial CSbC and axial CSbO angles are 114.95(10)°–126.82(11)° and 173.24(9)° (I), 117.2(2)°–122.9(2)° and 178.15(18)° (IIA), and 112.3(2)°–127.7(2)° and 175.09(18)° (IIB), respectively. The Sb-C and Sb-O bond lengths are 2.106(3)–2.182(3) and 2.1344(17) ÅI), 2.118(5)–2.4199(5) and 2.153(4)Å(IIA), and 2.106(5)–2.200(5) and 2.120(4) Å (IIB), respectively. A molecule of compounds I, IIA, and IIB has been found to contain Sb...N intramolecular contacts (2.838(3), 2.867(5), and 2.889(5)Å, respectively). Molecules of compounds IIA and IIB contain O-H...N hydrogen bonds (H...N, 1.91(9) and 2.06(8) Å, respectively).     

Amino Acid Esters Substituted Phosphorylated Emtricitabine and Didanosine Derivatives as Antiviral and Anticancer Agents

Owing to the promising antiviral activity of amino acid ester-substituted phosphorylated nucleosides in the present study, a series of phosphorylated derivatives of emtricitabine and didanosine substituted with bioactive amino acid esters at P-atom were synthesized. Initially, molecular docking studies were screened to predict their molecular interactions with hemagglutinin-neuraminidase protein of Newcastle disease virus and E2 protein of human papillomavirus. The title compounds were screened for their antiviral ability against Newcastle disease virus (NDV) by their in ovo study in embryonated chicken eggs. Compounds 5g and 9c exposed well mode of interactions with HN protein and also exhibited potential growth of NDV inhibition. The remaining compounds exhibited better growth of NDV inhibition than their parent molecules, i.e., emtricitabine (FTC) and didanosine (ddI). In addition, the in vitro anticancer activity of all the title compounds were screenedagainst HeLa cell lines at 10 and 100 μg/mL concentrations. The compounds 5g and 9c showed an effective anticancer activity than that of the remaining title compounds with IC₅₀ values of 40 and 60 μg/mL, respectively. The present in silico and in ovo antiviral and in vitro anticancer results of the title compounds are suggesting that the amino acid ester-substituted phosphorylated FTC and ddI derivatives, especially 5g and 9c, can be used as NDV inhibitors and anticancer agents for the control and management of viral diseases with cancerous condition.

Synthesis of some fused heterocyclic systems and their nucleoside candidates

A series of pyridofuro compounds were synthesized from 4-(4-chlorophenyl)-1,2-dihydro-2-oxo-6-(thiophen-2-yl)pyridine-3-carbonitrile (1) as starting material. Alkylation of 1 with ethyl bromoacetate gave the corresponding ester 2, which was condensed with hydrazine hydrate to afford the corresponding acid hydrazide derivative 3. Thrope-Ziegler cyclization of 2 with sodium methoxide gave furo[2,3-b]pyridine derivative 4, which was reacted with thiosemicarbazide, allyl isothiocyanate, formamide or hydrazine hydrate to give furopyridine derivatives 5–8, respectively. The latter compound 8 was cyclized with acetylacetone or formic acid to give the corresponding compounds 9 and 10, respectively. Furthermore, sulfurization of 1 with P₂S₅ gave the corresponding thioxopyridine 11, which was reacted with glycosyl (or galactosyl) bromide, morpholine or piperidine to give the corresponding thioglycoside 12a,b and Mannich base 14a,b derivatives. The deacetylation of 12a,b gave the corresponding deacetylated thioglycosides 13a,b, respectively. All the newly synthesized compounds were characterized by the elemental analyses and spectroscopic evidences (IR, ¹H- and ¹³C NMR).     

Evaluation of catalytic activity of imidazolo[1,2-a]pyridine derivatives: oxidation of catechol

A series of heterocyclic compounds possessing imidazolo[1,2-a]pyridine moiety, namely, ethyl 7-methylimidazolo[1,2-a] pyridine-2-carboxylate L1; 2-(3-nitrophenyl)imidazo[1,2-a]pyridine L2; 3-(imidazo[1,2-a]pyridine-2-yl)aniline L3; 2-phenylimidazolo[1,2-a]pyridine-3carbaldehyde L4; and 2-phenylimidazo[1,2-a]pyridine L5 were synthesized. The in situ generated copper (II), iron (II), and zinc (II) complexes of these compounds (L1–L5) were examined for their catalytic activities and were found to be effective catalysts for the oxidation of catechol to o-quinone with the atmospheric oxygen. The present study reveals that the rate of oxidation depends on four parameters: the nature of the ligand, transition metals, ion salts, and the concentration of the complex. The combination L2(Cu(CH ₃ COO) ₂ ) gives the highest rate.     

Synthesis and biological evaluation of novel triazole substituted pyrazolyl-methylenehydrazinyl-5-arylidene thiazolidinone derivatives as antibacterial and cytotoxic agents

Novel triazole substituted pyrazolyl-methylenehydrazinyl-5-arylidene thiazolidinone derivatives 6a–n and 7a–l were synthesized and characterized by Fourier transform infrared, ¹H and ¹³C nuclear magnetic resonance, mass spectrometry and elemental (CHN) analysis. The in vitro antibacterial (6a–n and 7a–l) and cytotoxic (6a–n) activities were evaluated for these compounds. The results revealed that the compounds 6b, 6i, 6k, 7b, 7h displayed good antibacterial activity. The compounds 6c (IC₅₀ = 5.4 μM), 6l (IC₅₀ = 6.3 μM) and 6f (IC₅₀ = 9.85 μM) were effective for inhibition of human breast cancer cell line MCF-7. Similarly, the compounds 6b (IC₅₀ = 8.7 μM) and 6c (IC₅₀ = 9.06 μM) were shown to have effective inhibition on human cervical cancer cell line Hela.     

Catalyst-free tandem Michael addition-cyclization reactions in aqueous media for the synthesis of benzimidazo[1,2-a]pyrimidinone derivatives

The catalyst-free reactions of Baylis-Hillman alcohols (1a-i) with 2-aminobenzimidazole (2) in THF-H₂O (1:4) were developed for the convenient and greener synthesis of benzimidazo[1,2-a]pyrimidinone derivatives (3a-i). The pesticidal activities of 3a-i were examined to investigate a new biological activity of the imidazo[1,2-a]pyrimidinone-type compounds.     

Enantioselective Supramolecular Carriers for Nucleoside Drugs. A Thermodynamic and Kinetic Gas Phase Investigation

The enantioselective interactions between chiral tetra-amidic receptors and nucleosides have been investigated by the ESI-IT-MS and ESI-FT-ICR-MS methodologies. Configurational effects on the CID fragmentation of diastereomeric [M ^H ₂ ?H?A]?⁺ aggregates (A?=?2'-deoxycytidine dC, citarabine (ara-C) were found to be mostly offset by isotope effect in [S ^X ₂ ?H?A]?⁺ (X?=?H, D) differently from the results obtained on the analogues (A?=?cytidine C and gemcitabine G). This result points the involvement of two different nucleoside/tetraamide isoforms. The structural differences of the [M ^H ₂ ?H?A]?⁺ (A?=?C and G) complexes vs. the [M ^H ₂ ?H?A]?⁺ (dC and ara-C) ones is fully confirmed by the kinetics of their uptake of the 2-aminobutane enantiomers, measured by FT-ICR mass spectrometry. Indeed, uptake of the 2-aminobutane enantiomers by [M ^H _n ?H?A]?⁺ (n?=?1,2; A?=?dC and ara-C) complexes is reversible, while that by [M ^H _n ?H?A]?⁺ (n?=?1,2; A?=?C and G) is not. The most encouraging result concerning the measured fragmentation and kinetic differences between C and ara-C, that are just epimers, indicates the possibility to subtly modulate the non-covalent drug/receptor interactions, through the electronic properties of the 2'-substituent on the nucleoside furanose ring, and furthermore on its three-dimensional position.     

Synthesis and antiproliferative activity in vitro of new 2-aminobenzimidazole derivatives. Reaction of 2-arylideneaminobenzimidazole with selected nitriles containing active methylene group

A series of pyrimido[1,2-a]benzimidazole and α-cyanocinnamic acid derivatives have been synthesized in the reactions of Schiff bases 2–7 with selected nitriles containing an active methylene group: malononitrile 8–12, cyanoacetamide 13–16, benzyl cyanide 17–21, benzoylacetonitrile 22–24, cyanoacetate methyl ester 25–28 and benzylacetamide 29. The structures 8–29 were confirmed by the results of elementary analysis and their IR, ¹H-, ¹³C-NMR and MS spectra. The products 8–29 of various chemical structure pyrimido[1,2-a] benzimidazole 8–12, 14–16, 17–21, 23–24, 26 and α-cyanocinnamic acid derivatives 13, 22, 25, 27, 28 were obtained, which are of interest for biological studies or which can be substrates for further synthesis. The selected compounds 10, 13, 14, 17, 19, 21, 23–25 and 28 were screened for their antiproliferative activity in vitro against neoplastic and normal cell lines. The most active two compounds were: 2-(o-bromophenylene)-3-cyano-4-phenyl-1,2-dihydropyrimido[1,2-a]benzimidazole (24) and 3-cyano-4-phenyl-2-(2,4-dimethoxyphenyl)-1,2-dihydropyrimido[1,2-a]benzimidazole (23). However, similarly like cisplatin used as the control, they showed no selectivity towards cancer cells, by inhibiting proliferation of normal mouse fibroblasts in similar manner.      

Synthesis of new transition metal complexes of 1H-perimidine derivatives having antimicrobial and anti-inflammatory activities

New series of 1H-perimidine-2-thiol derivatives and (2-substituted-1H-perimidin-1-yl)ethane-1,2-dione derivatives and their ligands (C₂₄H₁₄N₄S₂O₂) H₂L¹ and (C₂₆H₁₈N₄S₂O₂) H₂L² have been synthesized with transition metal ions, e.g., Copper (II), Silver (I), Cobalt (II) and Ruthenium (III) were prepared and evaluated for their antimicrobial, analgesic and anti-inflammatory activities. The synthesized compounds and their complexes were characterized by elemental analysis, ¹H NMR, IR, MS, molar conductance, thermal gravimetric analysis and electronic spectra. All results revealed that compounds 3 and 13 exhibited high inhibitory effects against some bacterial strains by the disc diffusion method. On the other hand, compounds 2, 3, 7 and 12 displayed potent anti-inflammatory activity.     

Syntheses, characterization and crystal structures of new mono- and bis-Schiff base compounds derived from 1,2,4-triazine and the silver(I) complexes containing mono-Schiff base ligands

Some new Schiff bases, (Z)-4-amino-3-((E)-(R-methoxybenzylidene)hydrazono)-6-methyl-3,4-dihydro-1,2,4-triazin-5(2H)-one (R?=?2 (L2), R?=?3 (L3) and R?=?4 (L4)), were synthesized by the condensation reactions of 4-amino-3-hydrazinyl-6-methyl-1,2,4-triazin-5(4H)-one (L1) and corresponding methoxybenzaldehyde in a molar ratio 1:1.5 in high yields. The reaction of L2 and L4 with an excess amount of the corresponding aldehydes gave the unsymmetrical bis-Schiff bases (E)-3-((E)-(R-methoxybenzylidene)hydrazono)-4-((E)-R-methoxybenzylideneamino)-6-methyl-3,4-dihydro-1,2,4-triazin-5(2H)-one (R?=?2 (L22) and R?=?4 (L44)), respectively. Furthermore, the reaction of L2?CL4 with silver(I) nitrate in a molar ratio 2:1 led to the silver(I)-complexes with the general formula [Ag(Lx)₂]NO₃ (Lx?=?L2 (2), L3 (3) and L4 (4)). All synthesized Schiff base compounds and complexes were characterized by a combination of IR-, ¹H-NMR spectroscopy, mass spectrometry and elemental analyses. In addition, the structures of L2, L4·CH₃CN, L22·CH₃OH and L44·CH₃OH and complexes 2 and 4 were determined by X-ray diffraction studies.     

A study of metal chelation of dinucleotide analogs in the gas phase by fast-atom bombardment mass spectrometry

Fast-atom bombardment (FAB) mass spectrometry was used to investigate the interaction of proton and alkali metal ions with dinucleotide analogs such as T-n-T (T = thymine moiety, n = polyether chain, e.g., triethylene, tetraethylene, pentaethylene, and hexaethylene ether 1–4), A-n-T (A = adenine unit 5–8), and T-n-OMe (9–12) in 3-nitrobenzyl alcohol matrix. The [M + H]⁺ ion is the most abundant ion for the A-n-T series, whereas in 1–4 and 9–12 the (TC₂H₄)⁺ ion is the most abundant. Formation of [M + H -C₂H₄O]⁺ ions, a characteristic fragmentation of crown ethers under electron ionization, is observed for compounds 1–12 and is more pronounced in 6 and 7. An abundant [M ? H]^? ion is observed for all the compounds studied under negative ion FAB due to the presence of the (-CO-NH-CO-) group of thymine, an indication of existence of intramolecular H bonding. The FAB mass spectra of 1–12 with alkali metal ions (Li⁺, Na⁺, K⁺, Rb⁺, and Cs⁺) showed formation of abundant metal-coordinated ions ([M + Met]⁺ and [TC₂H₄ + Met]⁺). Compounds 3, 4, 6, 7, and 10–12 showed ions due to the substitution of the thymine moiety by a hydroxyl group ([M + Met ? 108]⁺, Met = metal ion). For compound 3 alone, substitution of two thymine groups ([M + Met - 216]⁺) was observed. Metastable ion studies were used to elucidate the structures of these potentially significant ions, and the ion formule were confirmed with high resolution measurements. Selectivity toward metal complexation with ligand size was seen in the T-n-T and A-n-T series and was even more pronounced in A-n-T series. These dinucleotide analogs fall in the following order of chelation of alkali metal ions, acyclic glymes < dinucleotide analogs (acyclic glymes substituted with nitrogen bases) < crown ethers, which places them in perspective as receptor models.     

The Anticancer Activity and HSA Binding Properties of the Structurally Related Platinum (II) Complexes

The development of resistance and unwanted harmful interaction with other biomolecules instead of DNA are the major drawbacks for application of platinum (Pt) complexes in cancer chemotherapy. To conquer these problems, much works have been done so far to discover innovative Pt complexes. The objective of the current study was to evaluate the anti cancer activities of a series of four and five-coordinated Pt(II) complexes, having deprotonated 2-phenyl pyridine (abbreviated as C^N), biphosphine moieties, i.e., dppm?=?bis(diphenylphosphino) methane (Ph₂PCH₂PPh₂) and dppa?=?bis(diphenylphosphino)amine (Ph₂PNHPPh₂), as the non-leaving carrier groups. The growth inhibitory effect of the Pt complexes [Pt(C^N)(dppm)]PF₆: C ₁ , [Pt(C^N)(dppa)]PF₆: C ₂ , and [Pt(C^N)I(dppa)]: C ₃ , toward the cancer cell lines was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. In addition, the florescence quenching experiments of the interaction between human serum albumin (HSA) and the Pt complexes were performed in order to obtain the binding parameters and to evaluate the denaturing properties of these complexes upon binding to the general carrier protein of blood stream. The structure?Cactivity relationship studies reveal that four-coordinated Pt complexes C ₁ and C ₂ with both significant hydrophobic and charge characteristics, not only exhibit strong antiproliferation activity toward the cancer cell lines, but also they display lower denaturing effect against carrier protein HSA. On the other hand, five-coordinated C ₃ complex with the unusual intermolecular NH??Pt hydrogen binding and the intrinsic ability for oligomerization, exhibits poor anticancer activity and strong denaturing property. The current study reveals that the balance between charge and hydrophobicity of the Pt complexes, also their hydrogen binding abilities and coordination mode are important for their anticancer activities. Moreover, this study may suggest C ₁ and C ₂ as the potential template structures for synthesis of new generation of four-coordinated Pt complexes with strong anticancer activities and weak denaturing effects against proteins.     

Reaktionen mit phosphororganischen Verbindungen, 38. Mitt.: Zur Reaktivität von β-Cyanovinyl-triphenylphosphoniumbromid

β-Cyanovinyl-triphenylphosphonium bromide (1) rearranges to (2-cyano-1-phenylethyl)diphenylphosphine oxide (2) on treatment with alkali.1 reacts with NaN₃ to 5-triphenyl-phosphonium-1.2.3-triazole-ylide (3) and with cyclopentadiene to (5-cyano-bicyclo[2.2.1]hepten-2-yl-6)triphenylphosphonium bromide (4). Reaction of1 with thioamides leads to (α-cyano-β-amino-β-alkyl)-allyl-triphenylphosphonium hromides (6) together with [(2-alkyl-4-aminothiazolyl)-5-methyl]triphenylphosphonium bromides (5). (2-amino-3-imidazo[1.2—α]pyridinyl) methyl]triphenylphosphonium bromide (7) results from reaction of1 with 2-aminopyridine, [(2-amino-3-imidazo[1.2—α]pyrimidinyl)methyl]triphenylphosphonium bromides (8 and9) from 2-aminopyrimidine and 2-amino-4-6-dimethylpyrimidine resp.     

New N-nicotinyl and N-isonicotinyl, N′,N″-diaryl phosphorictriamides with new Er(III) complex: synthesis, spectroscopic study and crystal structures

Ten new N-nicotinyl and N-isonicotinyl phosphoramidates with formula XP(O)R₂, X?=?Nicotinamide(nia), R?=?NHCH₂Ph (1), N(CH₃)CH₂Ph (2), NHCH(CH₃)Ph (3), NH-CH₂C₄H₃O (4), NHCH₂(C₅H₄N) (5), 3-NH-C₅H₄N (6), and YP(O)R₂, Y?=?isonicotinamide(iso), R?=?NHCH₂Ph (7), N(CH₃)CH₂Ph (8), NHCH(CH₃)Ph (9), NH-CH₂C₄H₃O (10) plus one new Er(III) complex with formula Er(L)₂(NO₃)₃ (11), L?=?(iso)PO(NHCH₂C₄H₃O)₂ (10), were synthesized and characterized by elemental analysis and ¹H, ¹³C, ³¹P NMR, IR, UV?Cvis spectroscopy. Crystal structures of compounds 10 and 11 were also determined by X-ray crystallography. Interestingly, the ¹H NMR spectra of compounds 1, 2, 6, 7, 9 indicated long-range ⁿ J _P,H (n?=?5,6,7) coupling constants, in the range of 1.4?C1.9?Hz, for the splitting of pyridine ring protons with phosphorus atom. IR results showed that the ??(C=O) values of compounds 7?C10 are greater than those of compounds 1?C5 which means that isonicotinyl moiety is more electron withdrawing than nicotinyl group. X-ray outcomes revealed that in complex 11 three phosphoric triamide ligands have been connected to each Er(III); one from N_pyridine and two from P=O donor sites. One of the P=O donor ligands is mono dentate while the other one acts as a bidentate ligand and coordinates to another Er atom via its N_pyridine site. By forming complex 11 the P=O and C?CN_amide bond lengths of ligand is increased in both, mono and bi dentate, ligands while the C=O bond length is decreased to lower values. These variations are in good agreement with IR results. All H-bonds and electrostatic interactions lead to form a three-dimensional polymeric cluster in the crystal lattice of 10 and 11.     

Synthesis and anticancer activity of some new pyridine derivatives

Different substituents were introduced in positions 2 and 6 of 2,6 diaminopyridine in order to obtain new heterocyclic compounds. A new series of aza pyridine, imidazopyridine, benzodiazepine, indole, pyrimidine, and benzimidazole heterocyclic derivatives were synthesized in good yields. The anticancer activities of some of the new compounds were evaluated against liver cancer cell line HEPG2. Compounds 3, 4, 10, 11, 12, and 17 showed the highest activity when compared to 5-flurouracil (5-FU) and doxorubicin (DOX) chemotherapy.     

Copper(II), iron(III) and cobalt(III) complexes of the pendent-arm cyclam derivative 6,6,13-trimethyl-13-amino-1,4,8,11-tetraazacyclotetradecane

The interaction of Cu(II), Fe(III) and Co(III) with 6,6,13-trimethyl-13-amino-1,4,8,11-tetraazacyclotetradecane (L ³ ) incorporating a pendent amine group has led to isolation of the new octahedral complexes [Cu(HL ³ )(ClO₄)₂]Cl·H₂O (1), [Fe(L ³ )Cl](S₂O₆)·H₂O (2), [Co(L ³ )Cl](ClO₄)_1.5Cl_0.5·0.25H₂O (3), [Co(HL ³ )Cl₂](ClO₄)₂·H₂O (4) and [Co(L ³ )Cl]₂(S₂O₄)(ClO₄)₂ (5). In (1) the copper ion occupies the macrocyclic cavity of protonated (–NH₃ ⁺) L ³ which is present in its trans-III configuration; weakly bound ClO₄ ^? ligands occupy the axial positions. The X-ray structure of (2) showed that Fe(III) occupies the N₄-macrocyclic cavity of L ³ in a trans-III configuration, with the pendent amine group binding in an axial position. The remaining axial position is occupied by a Cl^? ligand. Chromatography of the product obtained from the reaction of Na₃[Co(CO₃)₃] with L ³ yielded three fractions. Fraction 1 yielded crystals (3) composed of three crystallographically independent species incorporating cations of type [Co(L ³ )Cl]²⁺ with very similar structures; in each case the macrocyclic ring nitrogens of L ³ are bound to the Co(III) in an asymmetric cis-fashion. Fraction 2 yielded the trans-III octahedral cationic complex (4) incorporating L ³ in its protonated form. The Co(III) complex (5) from fraction 3 shows a different coordination arrangement to the products from fractions 1 or 2. The macrocyclic ring coordinates in its trans-III form, but the axial sites in this case are occupied by the pendent-NH₂ group and a Cl^? ligand.     

Synthesis and structure of new copper(II) coordination compounds with 8-quinoline aldehyde semicarbazones and thiosemicarbazones

Copper(II) salts were reacted with various quinoline aldehyde chalcogensemicarbazones to yield compounds formulated as Cu(HL)X₂ · nH₂O (I: HL = quinoline aldehyde thiosemicarbazone (HL¹), X = ClO₄, n = 2; II: HL = quinoline aldehyde 4-C₂H₅-thiosemicarbazone (HL^1a), X = NO₃, n = 0; III: HL = quinoline aldehyde semicarbazone (HL²), X = ClO₄, n = 3 and IV: HL = quinoline aldehyde 4-Ph-semicarbazone (HL^2a), X = NO₃, n = 1). Regardless of the reagent ratio, the products were compounds having the metal: ligand ratio of 1: 1, where the organic ligand was coordinated tridentate in a molecular form. Single-crystal X-ray diffraction showed that, depending on the chalcogen atom in the organic ligand (S or O), the substituent in the 4th position (at the terminal nitrogen atom), and the specifics of the acido ligand, complexes I–IV had appreciably differing molecular structure organizations. The structures of I and III are formed by a 1D charged coordination polymer, ClO ₄ ^? anions, and water molecules and may be described by the formula [Cu(HL)(H₂O)(ClO₄)] _n (ClO₄) _n · nH₂O. Copper(II) coordination polyhedra in I and II are (4 + 2) and (4 + 1 + 1) tetragonal bipyramids, respectively. In II and IV, the structures are monomeric and can be described as [Cu(HL^1a)(NO₃)₂] with the metal coordination polyhedron shaped as a (4 + 1) tetragonal pyramid in II and as [Cu(HL^2a)(H₂O)(NO₃)](NO₃) with the metal coordination polyhedron shaped as a (3 + 2) trigonal bipyramid in IV. The structure of II is built of molecular complexes, each comprising, apart from ligand HL^1a, two monodentate coordinated NO ₃ ^? groups. The oxygen atom of one anion together with the NNS donor atom set of ligand HL^1a form the base, and the oxygen atom of the other anion is in the apex of the coordination polyhedron. In IV, the structure is ionic and built of NO ₃ ^? anions and [Cu(HL^2a)(H₂O)(NO₃)]⁺ complex cations, where a cationic coordination polyhedron has a trigonal-bipyramidal configuration with organic ligand HL^2a positioned along the long edge. The bipyramidal base is made up by the oxygen atoms of the coordinated water molecule and monodentate nitrato group and the nitrogen atom N2 of the azomethyne group.