Discovery of novel indole-based aroylhydrazones as anticonvulsants: Pharmacophore-based design

A number of novel melatonin derivatives, containing aroylhydrazone moieties, were synthesized and explored in vivo for anticonvulsant activity, neurotoxicity in ICR mice as well as in-vitro for cytoxicity and oxidative stress in rats. The structures and configurations were confirmed by NMR, FTIR, HRMS and crystal X-ray diffraction method. For selection of potent structures for synthesis a pharmacophore model was used. Two compounds 3e, with a 2-furyl moiety fragment and 3f with 2-thienyl fragment, showed a potency in maximal electroshock (MES) test (ED₅₀ = 50.98 mg kg⁻¹, PI > 5.88 and ED₅₀ = 108.7 mg kg⁻¹; PI > 2.76), respectively, higher than melatonin (ED₅₀ = 160.3 mg kg⁻¹, PI > 1.87). The compounds 3c, 3e, 3f and 3i suppressed psychomotor seizures in the 6 Hz test and 3c was the most potent with higher ED₅₀ = 13.98 mg kg⁻¹ and PI of > 21.46 compared to that of melatonin (ED₅₀ = 49.76 mg kg⁻¹ and PI of > 6.03) in mice. None of the compounds displayed neurotoxicity in the rota-rod test. The novel melatonin derivatives exerted weak cytotoxic effects while 3f showed the lowest hepatoxic effects comparable to that of the positive control melatonin in rats. The high affinities to the elucidated pharmacophore model of the novel melatonin compounds derived from the inclusion of aroylhydrazone moiety in the indole scaffold yielded suitable candidates with anticonvulsant activity in the MES and 6 Hz test of psychomotor seizures.     

Synthesis,molecular modelling studies and ADME prediction of benzothiazole clubbed oxadiazole-Mannich bases,and evaluation of their anti-diabetic activity through in vivo model

A small library of new benzothiazole clubbed oxadiazole-Mannich bases (M-1 to M-22) were synthesized and characterized by IR, NMR, Mass and Elemental analysis results. Molecular docking studies were done to assess the binding mode and interactions of synthesized hits at binding site of receptor Peroxisome proliferator-activated receptor, PPAR-γ or PPARG (PDB 1FM9). Among the synthesized compounds, nine compounds were selected on the basis of docking score and evaluated for their in vivo anti-diabetic activity using Oral Glucose Tolerance Test (OGTT) in normal rats followed by Streptozotocin (STZ) - induced diabetes. Results indicated that compound M-14 (161.39 ± 4.38) showed the highest reduction of blood glucose level comparable to that of the standard drug glibenclamide (140.29 ± 1.24) in STZ model. Other compounds exhibited moderate to good anti hyperglycaemic activity. ADME studies was done using Molinspiration online software, revealed that all compounds (except M-11) are likely to be orally active as they obeyed Lipinski’s rule of five.     

Synthesis,antimicrobial, cytotoxic and E. coli DNA gyrase inhibitory activities of coumarinyl amino alcohols

Here we report the in vitro antimicrobial activity (minimum inhibitory concentration) of fourteen coumarinyl amino alcohols 2–16 against eight bacterial strains and two fungi. Among these compounds 4, 8, 12, 15 and 16 showed moderate to good microbial inhibition with MIC values varied from 6.25 to 25 μg/mL. The most promising compounds were also evaluated for their in vitro cytotoxic and E. coli DNA gyrase inhibitory activities along with the two 7-oxy-4-methyl coumarinyl amino alcohol derivatives 17 and 18, which were found to be the most potent in in vitro antimicrobial screening in our previous study. All the active compounds, including 17 and 18, were also docked into the E. coli DNA gyrase ATP binding site (PDB ID: 1KZN) to investigate their binding interactions. Of these compound 17 has shown maximum binding energy value of −6.13 kcal/mol.     

Synthesis of aryl pyrazole via Suzuki coupling reaction,in vitro mushroom tyrosinase enzyme inhibition assay and in silico comparative molecular docking analysis with Kojic acid

Aryl pyrazoles are well recognized class of heterocyclic compounds found in several commercially available drugs. Owing to their significance in medicinal chemistry, in this current account we have synthesized a series of suitably substituted aryl pyrazole by employing Suzuki cross-coupling reaction. All compounds were evaluated for inhibition of mushroom tyrosinase enzyme both in vitro and in silico. Compound 3f (IC₅₀ = 1.568 ± 0.01 µM) showed relatively better potential compared to reference kojic acid (IC₅₀ = 16.051 ± 1.27 µM). A comparative docking studies showed that compound 3f have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (−6.90 kcal/mol) as compared to Kojic acid. The 4-methoxy group in compound 3f shows 100% interaction with Cu. Compound 3f displayed hydrogen binding interaction with His61 and His94 at distance of 1.71 and 1.74 Å which might be responsible for higher activity compared to Kojic acid.     

Imidazolo and tryptophan-imidazolo hybrid derived ureas/thioureas as potent bioactive agents – SAR and molecular modelling studies

Herein, we used an imidazole derivative (IMD) which showed promising antibacterial, antifungal and antioxidant properties in our earlier investigation. Prompted by this, we converted IMD to hydrazide (IMH) by hydrazinolysis which was derivatized to various ureas (3–7) and thioureas (8–12). On the other hand, IMH was conjugated to Boc-Trp-OH as it has been shown in the past that hybridization of two molecules produced promising biologically active compounds. Boc of the conjugate was removed and further converted into several urea (14–18) and thiourea (19–23) derivatives. All the title compounds so also the starting materials and intermediates were assessed for potential biological applications. The results showed that compounds 3, 4, 8, 9, 14, 15, 19 and 20 were excellent antioxidants as revealed by DPPH, DMPD and ABTS assays. Further, certain analogues like 5–7, 10–12, 16–18 and 21–23 were found to be potent antimicrobials against pathogenic bacteria and fungi whereas good anti-inflammatory activity was obtained for molecules 5–7, 10–12, 16–18 and 21–23. All together, derivatives of the conjugates have shown superior activity over non-conjugated compounds and the former have exhibited potent activity against standard drugs in all the assays. In a quest to understand the binding interactions of the compounds with active site of tyrosine kinase (PDB ID: 2HCK), glucosamine-6-phosphate (GlcN-6-P) synthase (PDB ID: 2VF5) and cyclooxygenase-2 (PDB ID: 1CX2) enzymes, the correlation studies were conducted using molecular modelling which showed good receptor binding interactions with several amino acids of the enzymes. Overall, the current investigation may be considered for the discovery of lead compound(s) for treating multiple disorder conditions using singular molecular entity.     

Drinks containing anthocyanin-rich blackcurrant extract decrease postprandial blood glucose,insulin and incretin concentrations

Blackcurrants are rich in polyphenolic glycosides called anthocyanins, which may inhibit postprandial glycemia. The aim was to determine the dose-dependent effects of blackcurrant extract on postprandial glycemia. Men and postmenopausal women (14 M, 9 W, mean age 46 years, S.D.=14) were enrolled into a randomized, double-blind, crossover trial. Low sugar fruit drinks containing blackcurrant extract providing 150-mg (L-BE), 300-mg (M-BE) and 600-mg (H-BE) total anthocyanins or no blackcurrant extract (CON) were administered immediately before a high-carbohydrate meal. Plasma glucose, insulin and incretins (GIP and GLP-1) were measured 0–120 min, and plasma 8-isoprostane F_2α, together with arterial stiffness by digital volume pulse (DVP) was measured at 0 and 120 min. Early plasma glucose response was significantly reduced following H-BE (n=22), relative to CON, with a mean difference (95% CI) in area over baseline (AOB) 0-30 min of −0.34 mmol/l.h (−0.56, −0.11, P<.005); there were no differences between the intermediate doses and placebo. Plasma insulin concentrations (AOB 0–30 min) were similarly reduced. Plasma GIP concentrations (AOB 0–120 min) were significantly reduced following H-BE, with a mean difference of −46.6 ng/l.h (−66.7, −26.5, P<.0001) compared to CON. Plasma GLP-1 concentrations were reduced following H-BE at 90 min. There were no effects on 8-isoprostane F_2α or vascular function. Consumption of blackcurrant extract in amounts roughly equivalent to 100-g blackcurrants reduced postprandial glycemia, insulinemia and incretin secretion, which suggests that inclusion of blackcurrant polyphenols in foods may provide cardio-metabolic health benefits. This trial was registered at clinicaltrials.gov as NCT01706653.     

Pyrazoles containing thiophene,thienopyrimidine and thienotriazolopyrimidine as COX-2 selective inhibitors: Design,synthesis, in vivo anti-inflammatory activity,docking and in silico chemo-informatic studies

New thiophene and annulated thiophene pyrazole hybrids were synthesized and screened for their in vitro COX-1/COX-2 enzymatic inhibition and in vivo anti-inflammatory activities. All compounds were more COX-2 selective inhibitors than COX-1 with compound 13 exhibiting the highest COX-2 selectivity index. Compounds 3, 6a, 9 and 11 were the most promising in the acute anti-inflammatory assay while compounds 3, 5, 6a, 6c, 9, 10, 11 and 13 exerted promising anti-inflammatory activity in the sub-acute anti-inflammatory assay. Compounds 3, 6a, 6c, 9, 10 and 11 were evaluated for their ED₅₀ values and were more potent than diclofenac sodium while compounds 6a, 6c and 9 were of greater potency than celecoxib with compound 6a being the most potent showing ED₅₀ = 0.033 mmol/kg. These compounds were non-toxic and proved to be gastrointestinal safe compared to indomethacin, diclofenac sodium and celecoxib. Docking studies into COX-2 active site (PDB code 3LN1) revealed that compounds 3, 6a, 6c, 9, 10, 11 and 13 had binding modes and energies comparable to that of celecoxib. Compounds 3, 9, 10 and 11 complied with Lipinski’s RO5 while compounds 6a and 6c showed one violation whereas compound 13 deviated by 2 violations. Compounds 6a, 6c and 13 showed 100% plasma protein binding (PPB) and showed no aqueous solubility while compounds 3, 10 and 11 demonstrated the best drug likeness model scores. Therefore, the thiophene analog 3 and the thienopyrimidine derivatives 10 and 11 are promising anti-inflammatory candidates that exert moderate selective COX-2 inhibition with acceptable physicochemical properties.     

An eco-friendly catalytic system for multicomponent,one-pot synthesis of novel spiro-chromeno indoline-triones and their anti-prostate cancer potentials evaluated via alkaline phosphatase inhibition mechanism

A green and efficient straightforward tactic for the one-pot regioselective synthesis of novel 10,10-dimethyl-9,10,11,11a-tetrahydro-6H-spiro[chromeno[4,3–b]chromene-7,3′-indoline]-2′,6,8 (7aH) -triones (4a-n) in one-pot modus has been established using eco-friendly p-toluenesulphonic acid as catalyst. Among the solvents that were used for synthesis, 4a-n were suitably synthesized with maximum yield (90–98%) in water. We avoided column purification and the formed by-product in the process is environmental-friendly. Hence, this reaction may consider as an astonishing piece work in this study, why because, the reaction mechanism that depends on the nature of the group attached to the isatin ring nitrogen atom. The main advantage of this protocol includes short reaction time, good yield, easy to work-up, practical simplicity, high regioselectivity and reduced pollutant, cost and avoids tedious purification. These pharmaceutically important compounds (4a-n) were recognized for their alkaline phosphatase inhibition and prostate cancer medication capabilities. The selective activity relation between alkaline phosphatase and prostate cancer was unveiled through the interaction of 4a-n to Human alkaline phosphatase (PDB ID: 1EW2).     

Synthesis,biological evaluation and molecular docking studies of novel 3,5-disubstituted 2,4-thiazolidinediones derivatives

A series of thirteen novel 2,4-thiazolidinedione derivatives were synthesized through three step reaction procedure. The title compounds were synthesized by Knoevenagel condensation at the 5th position of the 2,4-thiazolidinedione ring. Various physicochemical and spectral studies were conducted to characterize the synthesized derivatives including- IR, Mass, ¹H NMR, ¹³C NMR and elemental analysis. The derivatives were screened for in vivo anti diabetic, in vivo anti-inflammatory and in vitro free radical scavenging activities by carrageenan induced rat paw edema method, alloxan induced diabetes in wistar rats method and FRAP (ferric reducing antioxidant power) method respectively. Some of the derivatives emerged out as potent antidiabetic, anti inflammatory and free radical scavenging agents. Molecular docking was carried out to investigate some possible structural insights into the potential binding patterns of the most potent anti-diabetic molecules NB7,NB12 and NB13 with the active sites of target PPARγ (PDB ID: 2PRG) using MOE software. Dichloro derivative compound NB-7 has shown great potential in the present study as it not only has maximum antidiabetic activity but also possess excellent anti-inflammatory and antioxidant potential.     

Bis(diphenylphosphino)acetonitrile oxides, -sulfides and -imines: Their formation and structural features, and the remarkable structures of two lithiated derivatives

Oxidation of bis(diphenylphosphino)acetonitrile (dppmCN, 8) yields the corresponding bis-phosphinoxide system (9). Analogously, treatment of dppmCN with sulfur gave bis(diphenylphosphinsulfido)acetonitrile (10). Both compounds show very similar structures in the solid state, featuring strongly distorted U-shaped conformations. The Staudinger reaction of dppmCN with phenylazide gives rise to the formation of the bis(diphenylphosphinimino)acetonitrile product that was obtained in its ylidic P-NH tautomer form in solution and in the crystalline state. Deprotonation of the bis(diphenylphosphinchalcogenido)acetonitriles 9 and 10 gave the corresponding [NC-(Ph₂PX)₂]⁻ anions (X = O, S). Their lithio compounds show a remarkable structural diversity in dependence of the chalcogene element used. The oxygen-containing compound (13) forms an oxygen-coordinated Li⁺-bridged 12-membered heteromacrocyclic structure, whereas Li⁺ avoids sulfur coordination in 14 and exhibits a THF-stabilized Li⁺-NC-R adduct structure in the crystal.     

Development of novel synthesized phthalazinone-based PARP-1 inhibitors with apoptosis inducing mechanism in lung cancer

Herein we report the synthesis of two series of 4-phenylphthalazin-1-ones 11a-i and 4- benzylphthalazin-1-ones 16a-h as anti-lung adenocarcinoma agents with potential inhibitory activity against PARP-1. All the newly synthesized phthalazinones were evaluated for their anti-proliferative activity against A549 lung carcinoma cell line. Phthalazinones 11c-i and 16b, c showed significant cytotoxic activity against A549 cells at different concentrations (0.1, 1 and 10 μM) for two time intervals (24 h and 48 h). These nine phthalazinones were further examined for their inhibitory activity towards PARP-1. Compound 11c emerged as the most potent PARP-1 inhibitor with IC₅₀ value of 97 nM, compared to that of Olaparib (IC₅₀ = 139 nM). Furthermore, all these nine phthalazinones passed the filters of Lipinski and Veber rules, and predicted to have good pharmacokinetics properties in a theoretical kinetic study. On the other hand, western blotting in A549 cells revealed the enhanced expression of the cleaved PARP-1, alongside, with the reduced expression of pro-caspase-3 and phosphorylated AKT. In addition, ELISA assay confirmed the up-regulation of active caspase-3 and caspase-9 levels compared to the control, suggesting the activation of the apoptotic machinery in the A549 cells. Finally, molecular docking of 11c into PARP-1 active site (PDB: 5WRZ) was performed to explore the probable binding mode.     

Characterization of low-molecular-weight-glutenin subunit genes from the D-genome of Triticum aestivum,Aegilops crassa,Ae. cylindrica and Ae. tauschii

Twenty low-molecular-weight-glutenin subunit (LMW-GS) gene sequences from the D-genome from Aegilops crassa (2n = 4x = 28), Ae. cylindrica (2n = 4x = 28), Ae. tauschii (2n = 2x = 14) and Triticum aestivum (2n = 6x = 42) were obtained using five sets of specific allele primer pairs. Only the sequences of the first primer pair were complete coding sequences (cds) of LMW-GS, and had 305, 304, 306 and 305 LMW-m amino acid residues in Ae. crassa, Ae. cylindrica, Ae. tauschii and T. aestivum, respectively. The repetitive domain and repeat motif numbers of all LMW glutenin subunits showed eight conserved cysteine residues that lead to the same functional activity in different genome. Based on DNA and predicted protein sequences, phylogenetic trees for all sets of sequences were drawn. At the DNA level, the species closest to T. aestivum for the second, third, fourth and fifth set of sequences were Ae. cylindrica, Ae. tauschii and Ae. crassa, respectively. At the protein level, the species closest to T. aestivum based on the first, second and fifth set of sequences were Ae. cylindrica, Ae. crassa and Ae. crassa, respectively. For other sets of sequences, bread wheat proved to be a distinct species. The LMW-GS gene sequences have been recorded in the GenBank with accession numbers JQ726549–JQ726568JQ726549JQ726550JQ726551JQ726552JQ726553JQ726554JQ726555JQ726556JQ726557JQ726558JQ726559JQ726560JQ726561JQ726562JQ726563JQ726564JQ726565JQ726566JQ726567JQ726568.     

A fluorene-based diphosphinite ligand, its Ni, Pd, Pt, Fe, Co and Zn complexes and the first structurally characterized diphosphinate metal chelates

The diphosphinite ligand 9,9-(Ph₂POCH₂)₂-fluorene (1) was reacted with group 10 metal dichlorides to form chelate complexes of formula [MCl₂(1)] (MNi, 2; MPd, 3; MPt, 4) showing 8-membered metallocycles. Chloride abstraction from 3 with AgOTf afforded the dinuclear complex [M(μ-Cl)Pd(1)]₂(OTf)₂ (5), in which the ligand adopts a different conformation with respect of 3. In 5, the fluorene moiety and the phenyl groups display stabilizing interactions with the anion which is located close to the metal centre. With Fe(II), Co(II) and Zn(II) chlorides, the non-isolated intermediates [MCl₂(1)] readily undergo oxidation to [MCl₂(1_ox)] (MFe, 6; MCo, 7; MZn, 8; 1_ox = 9,9-(Ph₂P(O)OCH₂)₂-fluorene) in which the diphosphinate ligand and the metal centre form 10-membered metallocycles. Complexes 6-8 are the first examples of structurally characterized diphosphinate metal chelates. The Zn(II) diphosphinite complex [ZnCl₂(1)] (9) could be observed by NMR spectroscopy, along with the mixed phosphinite-phosphinate, mono-oxidized complex which is an intermediate in the formation of 8. Complex [ZnCl₂(9.9-fluorene-dimethanol)(Ph₂P(O)H)] (10) was also observed as hydrolysis product of 9. The X-ray molecular structures of 2, 3, 5.2OTf, 6, 7, 8 and 10 are reported.     

Amino acids conjugated quinazolinone-Schiff’s bases as potential antimicrobial agents: Synthesis,SAR and molecular docking studies

A series of amino acids conjugated quinazolinone-Schiff’s bases were synthesized and characterized by analytical and spectroscopic methods. All the synthesized analogues (8–43) and the intermediates (1–7) were screened for their in vitro antibacterial and antifungal activities. In antimicrobial activity, compounds 12–16, 21–25, 30–34 and 39–43 showed excellent antibacterial activity which is better than the antibacterial standard Streptomycin. Compounds 15, 23–25, 30–34, 36 and 38–43 showed excellent antifungal activities which is more active than the reference antifungal drug Bavistin. Further, to understand the correlation of biological activity with that of drug-receptor interaction, molecular docking was performed on active site ofglucosamine-6-Phosphate (GlcN-6-P) synthase (PDB ID: 2VF5) which showed good binding profile. Molecular docking studies and Preliminary structure-activity (SAR) relationship revealed that the tryptophan and phenylalanine conjugated quinazolinones with electron donating groups (OH and OCH₃) were found to be excellent antimicrobial activities which is better than the glycine and alanine conjugated derivatives. This may be explained by the contribution of aromaticity and hydrophobicity of amino acids. Among the series, compounds 41 and 43 showed the highest docking scores for antimicrobial activity. The conjugation plays a major role in improving the biological activities of those compounds.     

A new cumulene diiron complex related to the active site of Fe-only hydrogenases and its phosphine substituted derivatives: synthesis, electrochemistry and structural characterization

A new cumulene diiron complex related to the Fe-only hydrogenase active site [(μ-SCH₂C(S)CCH₂)Fe₂(CO)₆] (1) was obtained by treatment of (μ-LiS)₂Fe₂(CO)₆ with excess 1,4-dichloro-2-butyne. By controllable CO displacement of 1 with PPh₃ and bis(diphenylphosphino)methane (dppm), mono- and di-substituted complexes, namely [(μ-SCH₂C(S)CCH₂)Fe₂(CO)₅L] (2: L = PPh₃; 3: L = dppm) and [(μ-SCH₂C(S)CCH₂)Fe₂(CO)₄L₂] (4: L = PPh₃; 5: L = dppm) could be prepared in moderate yields. Treatment of 1 with bis(diphenylphosphino)ethane (dppe) afforded a double butterfly complex [(μ-SCH₂C(S)CCH₂)Fe₂(CO)₅]₂(μ-dppe) (7). With dppm in refluxing toluene, a dppm-bridged complex [(μ-SCH₂C(S)CCH₂)Fe₂(CO)₄(μ-dppm)] (6) was obtained. These model complexes were characterized by IR, ¹H, ³¹P NMR spectra and the molecular structures of 1, 2 and 5-7 were determined by single crystal X-ray analyses. The electrochemistry of 1-3 was studied and the electrocatalytic property of 1 was investigated for proton reduction in the presence of HOAc.     

Coordination and derivatization of 3, 4, and 6-membered nitrogen heterocycles at a chiral tungsten(II) center

Reaction of [Tp′W(CO)₂(PhCCPh)][OTf] (1b) (Tp′ = hydridotris(3,5-dimethylpyrazolyl)borate) with excess aziridine or 2-methylaziridine followed by protonation with produces chiral tungsten(II) amine complexes (3, 4; R = Me, Ph). An azetidine amido complex, Tp′W(CO)(PhCCMe)(H₂) (5) is synthesized by reaction of [Tp′W(CO)₂(PhCCMe)][OTf] (1a) with excess azetidine. Oxidation of amido complex 5 with I₂ in the presence of a weak base provides the corresponding 1-azetine complex, (6). Addition of methylmagnesium bromide to complex 6 results in formation of predominantly one diastereomer (S_WR_C/R_WS_C) (96:4 dr) of the 2-methylazetidine complex, Tp′W(CO)(PhCCMe)(H₂) (7). Reaction of complex 5 with results in formation of a cationic azetidine complex, (8). Reaction of 1b with excess piperidine followed by oxidation affords 2,3,4,5-tetrahydropyridine complex 9b, . Formation of an enamido complex, Tp′W(CO)(PhCCPh)(H₂) (10), is observed upon addition of base to 9b. Subsequent addition of [D⁺] to the enamido β-carbon results in the formation of the deuterated product, 9b-d₁, as determined by ²H NMR. Seven X-ray crystal structures have been determined, and these encompass complexes with 3, 4, and 6-membered heterocyclic ligands. Crystal structures are reported for two aziridine adducts (2, 4) two neutral amido complexes (5, 7), one cationic imine complex (6), and one cationic amine (8) complex derived from azetidine, and the imine complex formed from piperidine (9).     

Design,synthesis and molecular docking of new N-4-piperazinyl ciprofloxacin-triazole hybrids with potential antimicrobial activity

New N-4-piperazinyl ciprofloxacin-triazole hybrids 6a-o were prepared and characterized. The in vitro antimycobacterial activity revealed that compound 6a experienced promising antimycobacterial activity against Mycobactrium smegmatis compared with the reference isoniazide (INH). Additionally, compound 6a exhibited broad spectrum antibacterial activity against all the tested strains either Gram-positive or Gram-negative bacteria compared with the reference ciprofloxacin. Also, compounds 6g and 6i displayed considerable antifungal activity compared with the reference ketoconazole. DNA cleavage assay of the highly active compounds 6c and 6h showed a good correlation between the Mycobactrium cleaved DNA gyrase assay and their in vitro antimycobactrial activity. Moreover, molecular modeling studies were done for the designed ciprofloxacin derivatives to predict their binding modes towards Topoisomerase II enzyme (PDB: 5bs8).     

Synthesis, structure, and catalytic ethylene oligomerization of nickel(II) and cobalt(II) complexes with symmetrical and unsymmetrical 2,9-diaryl-1,10-phenanthroline ligands

A series of nickel(II) and cobalt(II) complexes, NiX₂L (X = Cl, Br; 1-6) and CoCl₂L (7-9), with 2,9-diaryl-1,10-phenanthroline ligands (L¹-L³) have been synthesized and characterized by elemental analysis, UV-Vis, IR spectroscopy, and X-ray crystal structural study (for 1, 4-7, 9). The solid-state structures of 1, 5-7 and 9 show four-coordinate, slightly flattened tetrahedral geometry at the Ni(II) or Co(II) center, while 4 is five-coordinated (square-pyramidal), containing a THF molecule as an auxiliary ligand. The title complexes (1-9) display good catalytic activities in ethylene oligomerization when activated with methylaluminoxane (MAO). While the Co(II) precatalysts produce primarily C₄ isomers, the Ni(II) complexes give ethylene dimers and trimers at normal pressure. The activities and yields of linear α-olefins increase with increasing ethylene pressure for the Ni(II) complexes, leading to more high-molar-mass products (C₈-C₁₈). Complex 6 displays the best catalytic activity among the complexes studied (up to 1518 kg/mol[Ni] h at 10 atm).     

Synthesis,characterization and in silico designing of diethyl-3-methyl-5-(6-methyl-2-thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamido) thiophene-2,4-dicarboxylate derivative as anti-proliferative and anti-microbial agents

A series of eight compounds diethyl-3-methyl-5-(6-methyl-2-thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamido) thiophene-2,4-dicarboxilate (KM_10–17) analogues have been prepared by conventional methods and characterized by IR, Mass, NMR and elemental analysis. In silico docking studies on Human topoisomerase IIbeta (PDB Id: 3QX3) have been performed for all molecules (KM_10–17) synthesized. The compounds were tested for in vitro anti-proliferative activity on VERO and 786-O cell lines. Out of all the synthesized compounds, KM₁₁ & KM₁₆ showed moderate activity on both cell lines. In vitro anti-microbial activity was also checked against Bacillus subtilis (BS), Staphylococcus aurous (SA), Pseudomonas aeruginosa (PA), Escherichia coli (EC) and Candida albicans (CA) by well diffusion method. The compound KM₁₁ was found to have highest zone of inhibition against BS, SA, PA and EC. The molecules KM₁₃ and KM₁₆ exhibited good activity against CA. The compounds KM₁₄ and KM₁₆ indicated good zone of inhibition against BS.     

Syntheses, structures, and mesomorphic properties of two series of oxovanadium(IV) salen and salpn complexes with 4-substituted long alkoxy chains

Two series of oxovanadium(IV) salen and salpn complexes containing 4-substituted alkoxy chains of aromatic rings, [VO((4-C_nH_2n+1O)₂salen)] (n = 3 (1), 4 (2), 6 (3), 8 (4), 10 (5), 12 (6), 14 (7), 16 (8), 18 (9), and 20 (10) and salen = N,N′-ethylenebis(salicylideneiminato)), and [VO((4-C_nH_2n+1O)₂salpn)] (n = 8 (11), 10 (12), 12 (13), 14 (14), 16 (15), and 18 (16) and salpn = N,N′-propylenebis(salicylideneiminato)), have been prepared and their mesomorphic properties have been investigated. The crystal structures of 1-9 except for 7 by an X-ray crystallographic analysis have been revealed. Complexes 4-9 in the solid state have been confirmed as novel bilayer crystal structures composed of only the VO(IV) complex without linear chains via the VO units. The VO(IV) complexes with longer alkoxy chains of 8-10 transferred from the bilayer crystal to the bilayer metallomesogens (liquid crystals). Based on the X-ray analyses and the precise extinction rules for 8-10 with the bilayer metallomesogens, complexes 8-10 were identified as the liquid crystalline (M(Pa2₁)) phase derived from 80 layer groups. On the other hand, the 4-alkoxysalpn complexes of 14-16 showed the unusual rectangular columnar mesophase (Col_r) with the linear chain via the VO units supported by the existence of the VO stretching band characteristic of weak linear chain formation via the VO units in the liquid crystal.