Derivatives 4a-j Research Articles

Synthesis and antimicrobial evaluation of some new hydrazo, dihydropyridazinyl and triazolyl derivatives containing indole nucleus

PurposeThe aim of this paper is synthesis of some new hydrazo, dihydropyridazinyl and triazolyl derivatives containing indole nucleus and their antimicrobial evaluation.Design/methodology/approachTreatment of 3-(1H-indol-3-yl)-3-oxopropanenitrile (1) with different aryl diazonium salts 2a-j gave the corresponding arylazohydrazone derivatives 3a-j. The azo derivatives 3d and 3e were used as the key intermediate for the synthesis of some new diazines 5d, e and triazoles 7d, e. The newly synthesized compounds were characterized by electronic absorption properties – IR, 1HNMR and MS studies – and screened for their biological evaluation. Compounds 3a-j, 5d, e and 7d, e showed promising results as antimicrobial agents.FindingsCompounds 3a-j, 5d, e and 7d, e showed promising results as antimicrobial agents.Originality/valueNo details regarding the synthesis of such dyes are reported before in the literature.

Design, synthesis, structural elucidation and antimicrobial screening of novel 1, 5-benzothiazepine derivatives derived from thieno [3, 2-d] pyrimidine nucleus

1, 5-Benzo Thiazepine is the Main Seven membered Heterocyclic ring systems reported for their cardiac and Psychotherapeutic activities.1, 5 Benzo Thiazepines were highlighted as important Biologically active Scaffolds. In This Article New series of benzo [b] [1, 5]-thiazepine derivatives 6 a-j were synthesized by applying the cyclo condensation of (E)-3-(thieno [3, 2-d] pyrimidin-6-yl)-1-p-Substituted prop-2-en-1-one derivatives 4a-j with 2amino thio phenol (5) in DMF. The new intermediate Chalcone derivatives 4a-j were obtained from interaction of various P-substituted Acetophenone & Heterocyclic Acetyl derivatives 3(a-j) and thieno[3, 2-d]pyrimidine-7carbaldehyde. The synthesized 1, 5-benzothiazepines 6a-j have been screened for their antimicrobial activity. From anti-bacterial and anti-fungal activity screening results, it has been observed that compounds 6h, 6e, 6i and 6d possess good activity.

Design, synthesis, and anticancer activity of C8-substituted-4′-thionucleosides as potential HSP90 inhibitors

A series of C8-substituted-4′-thioadenosine analogs 3a–3g, 15, and 17 and their truncated derivatives 4a–4j, 23–25, and 27 have been successfully synthesized from d-ribose and d-mannose, respectively, employing Pummerer type or Vorbrüggen condensation reactions and the functionalization at the C8-position of nucleobase via Stille coupling or nucleophilic aromatic substitution reactions as key steps. All the synthesized compounds were assayed for their HSP90 inhibitory activity, but they were found to be inactive up to 100μM. However, the 8-iodo derivatives 15, 17, and 27 exhibited potent anticancer activity, indicating that different mechanism of action might be involved in their biological activity.

Synthesis, cytotoxic, anti-lipoxygenase and anti-acetylcholinesterase capacities of novel derivatives from harmine

We synthesized two series of new hydrazide harmine derivatives. The reaction of harmine 1 with ethyl acetate chloride afforded the corresponding ethyl ester 2. The treatment of 2 with hydrazine hydrate gave the hydrazide 3 which further converted into hydrazones 4a–j and dihydrazides 5a–c. A series of new triazoles 7a–f has also been prepared from the suitable propargyl harmine 6. The synthesized derivatives were characterized by 1H-NMR, 13C-NMR, and HRMS and evaluated for their activities against MCF7, HCT116 OVCAR-3, acetylcholinesterase and 5-lipoxygenase. The most hydrazones derivatives 4a-j have a good cytotoxic activity against all cell lines, when 4a, 4d, 4f and 4 g are more active than 1 (against OVCAR-3 IC50 16.7–2.5 μM). The compound 6 was the most active (IC50 = 1.9 μM) against acetylcholinesterase. Some compounds exhibited significant activity against 5-lipoxygenase (IC50 = 30.9–63.1 μM).

Synthesis, anti-microbial and anti-cancer evaluation study of 3-(3-benzofuranyl)-coumarin derivatives

The series of 3-coumarin-substituted benzofuran derivatives 4a–4j have been synthesized under optimized experimental condition with excellent yields. All the isolated compounds were characterized and screened anti-microbiological and anti-cancer activity. The anti-microbiological results observed were extremely good against S. aureus, C. albicans and A. niger. The comparative docking studies with gyrase type IIA topoisomerase from mycobacterium tuberculosis docked with ligands and 4j have found lowest docked energy.

Synthesis of N-Mannich bases of berberine linking piperazine moieties revealing anticancer and antioxidant effects.

A new Mannich base series of piperazine linked berberine analogues was furnished in this study to screen the antioxidant and anticancer potential of the resultant analogues. Alkoxy group at a C-9 position of berberine was converted to hydroxyl functionality to enhance the ability of final scaffolds binding to the target of drug action mainly through hydrophobic effect, conjugation effect, whereas Mannich base functionality was introduced on the C-12 position of berberine. Scaffolds were investigated for their free radical scavenging antioxidant potential in FRAP and DPPH assay, whereas tested to check their Fe+3 reducing power in ABTS assay. The radical scavenging potential of the final derivatives 4a–j was found excellent with IC50s, <13 μg/mL and < 8 μg/mL in DPPH and ABTS assay, respectively, whereas some analogues showed significant Fe+3 reducing power with absorption at around 2 nm in the FRAP assay. Anticancer effects of titled compounds were inspected against cervical cancer cell line Hela and Caski adapting SRB assay, in which analogues 4a–j presented <6 μg/mL of IC50s, and >30 of therapeutic indices, thus exerting low cytotoxic values against Malin–Darby canine kidney (MDCK) cell lines at CC50s >125 μg/mL. Hence, from the bioassay outcomes it can be stated that these analogues are dual active agents as the scavengers of reactive oxygen species and inhibitors of the cancerous cells as compounds with halogen functional group have overall good pharmacological potential in assays studied in this research. Correct structure of the final compounds was adequately confirmed on the basis of FT-IR and 1H NMR as well as elemental analyses.

Ultrasound-assisted synthesis, anticonvulsant activity, and docking study of indole-appended thiazolidin-4-ones.

Two series of novel indolyl thiazolidin-4-one derivatives 4a-j and 5a-j were obtained by an ecofriendly synthetic protocol by treating a mixture of Schiff's bases (0.01 mol) with thioglycolic acid or thiolactic acid (0.01 mol) and anhydrous zinc chloride in catalytic amount in DMF as solvent under ultrasound irradiation, using an ultrasound synthesizer with a synthetic solid probe. The structures of the synthesized compounds were confirmed by IR, (1) H NMR, (13) C NMR, MS, and elemental analysis. The anticonvulsant activity and neurotoxicity of the newly synthesized compounds were established by MES and sc-PTZ model and by rotarod test, respectively, in vivo using mouse models. The actophotometer was used for the screening of behavioral activity. The compounds exhibited promising anticonvulsant activity; especially, the compounds showed maximum protection in the MES model at a dose of 100 mg/kg. Further, docking studies of the synthesized compounds were performed against the sodium channel receptor and showed good binding interactions with the receptor. A computational study was carried out to highlight the pharmacophore distance mapping, log p determination, and pharmacokinetic parameters.

Synthesis and Pharmacological Screening of Novel meso‐Substituted Porphyrin Analogs

A novel series of mesotetrakis[aryl]-21H,23H-porphyrin derivatives 2a-j was synthesized from the condensation of aldehyde derivatives 1a-j with pyrrole in the presence of p-toluenesulfonic acid. The synthesized porphyrins were considered as a model to study the free radical-induced damage of biological membranes and the protective effects of these porphyrins. It was found that these compounds effectively inhibit the free radical-induced oxidative hemolysis of red blood cells. Compounds 2c and 2d which bear a sulfur atom, a nitro group, and a chlorine atom exhibited markedly higher antihemolysis activity than the other analogous. Compounds 2a, 2c, 2d, and 2j showed the highest protection activity against DNA damage induced by the bleomycin-iron complex. Compounds 2d, 2f, 2i, and 2j were proved to exhibit antioxidative activity.

Synthesis and Biological Activity of Some Novel Phenyl Pyrazoline Derivatives

A new series of 4-(4-hydroxyphenyl)-3-chloro-1-{4-(5-(substituted phenyl)-1-phenyl- 4,5- dihydro-pyrazol-3-yl)phenyl}azetidin-2-one were synthesized by reacting 3-chloro-1-{4-(3- (substituted-phenyl)prop-2-enoyl)phenyl}-4-(4-hydroxyphenyl)azetidin-2-one (0.01 M) and phenyl hydrazine (0.01 M) in presence of acetic acid (glacial). All these compounds were characterized by means of their IR, 1 H NMR, spectroscopic data and microanalysis. All the synthesized products were evaluated for their antimicrobial activity. All the compounds were tested for their antibacterial and antifungal activities by broth dilution method. 14-17 . In the present study, the reaction of 3- chloro-1-{4-(3-(substituted phenyl) prop-2-enoyl) phenyl}-4-(4-hydroxyphenyl) azetidin-2- one with phenyl hydrazine in presence of acetic acid (glacial) to form pyrazoline derivatives 4a-j (Scheme 1). The structures of the various synthesized compounds were assigned on the basis of IR, 1 H NMR spectral data and elemental analysis. These compounds were also screened for their antimicrobial activity.

ChemInform Abstract: Synthesis and Biological Screening of Some Novel Amidocarbamate Derivatives of Ketoprofen.

A series of novel ketoprofen derivatives 4a-j bearing both amide and carbamate functionalities were prepared using benzotriazole. Selective reduction of ketoprofen produced hydroxy derivative 2, which reacts with one or 2 mol of 1-benzotriazole carboxylic acid chloride (1) gave benzotriazole derivatives 3a and 3b respectively. Antioxidative screenings revealed that the prepared compounds 3b and 4a-j possess excellent lipid peroxidation inhibition at 0.1 mM concentration. Two of the compounds 3b and 4 g also showed high soybean lipoxygenase inhibition activity, where as the amidocarbamate derivatives of ketoprofen showed only weak reducing activity against 1,1-diphenyl-2-picrylhydrazyl radicals. No selective antiviral effects were noted for the tested compounds against a broad variety of DNA and RNA viruses.

Characterization of new PPARγ agonists: Benzimidazole derivatives—importance of positions 5 and 6, and computational studies on the binding mode

In this and previous studies we investigated the importance of partial structures of Telmisartan on PPARgamma activation. The biphenyl-4-ylmethyl moiety at N1 and residues at C2 of the central benzimidazole were identified to be essential for receptor activation and potency of receptor binding. Now we focused our attention on positions 5 and 6 of the central benzimidazole and introduced bromine (3b-5/6, 3c), phenylcarbonyl (3d-5/6), hydroxy(phenyl)methyl (3g-5/6), hydroxymethyl (3h-5/6) and formyl (3i) groups. The selection of these moieties was inspired by the structure of Losartan and its metabolite EXP3179. In order to increase the hydrophobicity of the central part of the molecule, the benzimidazole was exchanged by a naphtho[2,3-d]imidazole (5). The compounds 3a-3i and 5 were tested in a differentiation assay using 3T3-L1 preadipocytes and a luciferase assay using COS-7 cells, transiently transfected with pGal4-hPPARgammaDEF, pGal5-TK-pGL3 and pRL-CMV, as established models for the assessment of cellular PPARgamma activation. An enhanced effect on PPARgamma activation could be observed if lipophilic moieties are introduced in these positions. 4'-[(2-Propyl-1H-naphtho[2,3-d]imidazol-1-yl)methyl]biphenyl-2-carboxylic acid (5) was identified as the most potent compound with an EC(50) of 0.26muM and the profile of a full agonist. Together with compounds of the former structure-activity relationship study (position 2-substituted benzimidazole derivatives 4a-4j), the binding mode of Telmisartan and its derivatives have been analyzed in 3D pharmacophore-driven docking experiments.

RETRACTED: Synthesis and biological screening of some novel amidocarbamate derivatives of ketoprofen

A series of novel ketoprofen derivatives 4a-j bearing both amide and carbamate functionalities were prepared using benzotriazole. Selective reduction of ketoprofen produced hydroxy derivative 2, which reacts with one or 2 mol of 1-benzotriazole carboxylic acid chloride (1) gave benzotriazole derivatives 3a and 3b respectively. Antioxidative screenings revealed that the prepared compounds 3b and 4a-j possess excellent lipid peroxidation inhibition at 0.1 mM concentration. Two of the compounds 3b and 4 g also showed high soybean lipoxygenase inhibition activity, where as the amidocarbamate derivatives of ketoprofen showed only weak reducing activity against 1,1-diphenyl-2-picrylhydrazyl radicals. No selective antiviral effects were noted for the tested compounds against a broad variety of DNA and RNA viruses.

The novel amidocarbamate derivatives of ketoprofen: synthesis and biological activity

A series of novel ketoprofen derivatives 4a–j bearing both amide and carbamate functionalities were prepared using the benzotriazole method of carboxylic and hydroxy group activation. Selective reduction of ketoprofen produced hydroxy derivative 2, which in the reaction with one or two moles of 1-benzotriazole carboxylic acid chloride (1) gave benzotriazole derivatives 3a and 3b, respectively. Compounds 3a and 3b with various amines afforded amidocarbamates 4a–j. Antioxidative screenings revealed that the prepared compounds 3b and 4a–j possess excellent lipid peroxidation inhibition at 0.1 mM concentration, higher than 95% for the derivatives bearing aromatic, cycloalkyl or heterocyclic substituents. Two of the compounds, 3b and 4g, also show high soybean lipoxygenase inhibition activity (95 and 83.5%, respectively). On the other hand, the amidocarbamate derivatives of ketoprofen show only weak reducing activity against 1,1-diphenyl-2-picrylhydrazyl radicals. No selective antiviral effects were noted for the tested compounds against a broad variety of DNA and RNA viruses. Most compounds were endowed with a moderate (IC50: 10–25 μM) cytostatic activity.

Synthesis, anticancer, and anti-inflammatory activity evaluation of methanesulfonamide and amidine derivatives of 3,4-diaryl-2-imino-4-thiazolines

Condensation of 3,4-diaryl-2-imino-4-thiazoli-nes 1a-j with methanesulfonyl chloride gave methanesulfonamide derivatives 2a-j. Condensation of 2-cyanopyrazine, 4-cyanopyridine, and 2-cyanopyridine with 3,4-diaryl-2- imino-4-thiazolines 1h-m in the presence of sodium methoxide afforded amidine derivatives 3a-j. Compounds 2a-j and 3a-j were screened against various human cancer cell lines (COLO-205, HEP-2, A-549, IMR-32) and their percentage growth inhibition profile determined at 1 x 10(-5)M. The anti-inflammatory activity of these compounds was assessed using the carrageenan-induced paw edema model. Compound 2i exhibited 34.7% anti-inflammatory activity at 50 mg/kg p.o., which is comparable to standard care drug phenyl butazone (37% activity at 50 mg/kg p.o.).

Synthesis and biological evaluation of some new pyrimidines via a novel chalcone series

In the present investigation ethyl 2-(4-carboxyphenylazo)acetoacetate 1 on condensation with various aromatic aldehydes in ethanolic NaOH solution yielded the corresponding chalcones 2a-j. These chalcones were further reacted with urea in the presence of base in ethanol, which led to the formation of pyrimidine derivatives 3a-j. The newly synthesized heterocyles were characterized on the basis of their chemical properties and spectroscopic data. All newly synthesized compounds were evaluated for their antimycobacterial activities against Mycobacterium tuberculosis H37Rv.

Synthesis of New Pyrazolothiazole Derivatives from 4-Thiazolidinones

The synthesis of new 2,3,5,6-aryl substituted tetrahydro-2H-pyrazolo[3,4-d]- thiazoles 4a-j as potential biologically active compounds by the cyclocondensation of phenyl hydrazine with new 5-arylidene derivatives 2a-j of 2,3-disubstituted-1,3- thiazolidin-4-ones 1a-e is reported.

Synthesis of Some Novel Ethyl 5‐Methyl‐6‐cyano‐7‐substituted‐2‐oxo‐2H‐pyrano [2,3‐b]pyridine‐3‐carboxylate Derivatives.

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Synthesis and Evaluation of Quindoline Derivatives as G-Quadruplex Inducing and Stabilizing Ligands and Potential Inhibitors of Telomerase

A new series of quindoline derivatives (4a-j) were designed and synthesized to develop novel and potent telomerase inhibitors. The interaction of the G-quadruplex of human telomere DNA with these newly designed molecules was examined via circular dichroism spectroscopy and electrophoretic mobility shift assay (EMSA). The selectivity between the quindoline derivative (4a) and G-quadruplex or duplex DNA was investigated by competition dialysis. These new compounds as inhibitors of telomerase were also investigated through the utilization of modified telomerase repeat amplification protocol (TRAP) assay. The results revealed that the introduction of electron-donating groups such as substituted amino groups at the C-11 position of quindoline significantly improved the inhibitory effect on telomerase activity ((Tel)IC50 > 138 microM for quindoline, 0.44-12.3 microM for quindoline derivatives 4a-j). The quindoline derivatives not only stabilized the G-quadruplex structure but also induced the G-rich telomeric repeated DNA sequence to fold into quadruplex.

Synthesis of Pyrazole Imines and Azetidinone Compounds Using Conventional and Microwave Technique and Studies of Their Antibacterial Activity.

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Synthesis of Novel Schiff Base and Azetidinone Derivatives and their Antibacterial Activity

A series of Compound 4‐(2᾽‐hydroxy‐3᾽‐chloro‐5᾽‐ethyl phen‐1᾽‐yl)‐1‐(4᾽‐tolyl)‐3‐chloro‐2‐azetidinone 4a‐j have been prepared by the reaction of 2 ‐hydroxy‐3 ‐chloro‐5 ‐ethyl‐N‐(p‐tolyl)‐chalconimines 3a‐j with chloroacetyl chloride in the presence of triethylamine. The Schiff base derivatives 3a‐j has been prepared by the condensation of different substituted chalone derivatives 1 with p‐toluidine 2. The synthesized compounds were screened for their antibacterial activity against Staphylococcus aureus and Escherichia coli.