Synthesis, Analgesic, and Antiparkinsonian Profiles of Some Pyridine, Pyrazoline, and Thiopyrimidine Derivatives

Summary. A series of substituted pyridine, pyrazoline, and thiopyrimidine derivatives were synthesized from 3-acetylpyridine, which was prepared from nicotinic acid as a naturally starting material. The pharmacological screening showed that many of these compounds have good analgesic and antiparkinsonian activities comparable to Voltarene^? and Benzatropine^? as reference drugs. The structure assignment of the new compounds is based on chemical and spectroscopic evidence. The detailed synthesis, spectroscopic data, and pharmacological properties for synthesized compounds are reported.     

Synthesis of some thiopyrimidine and thiazolopyrimidines starting from 2,6-dibenzylidene-3-methylcyclohexanone and its antimicrobial activities

A series of novel N-substituted arylidene, pyrazole, thioxopyrimidine and thiazolopyrimidine derivatives 2–7 were synthesized by initial reactions of 2-methyl-cyclohexanone with aromatic aldehydes to give 2,6-dibenzylidene-3-methylcyclohexanone 2. Some of the synthesized compounds were tested as antimicrobial agents. The detailed synthesis, spectroscopic data, and antimicrobial activities of the synthesized compounds were reported.     

Synthesis,Reactions, and Pharmacological Activities of Some Pyrimidines Using (<Emphasis Type="Italic">N</Emphasis>-Methylindolyl)acetic Acid as Synthon

Summary. A series of pyrimidinones, thienopyrimidines, and their derivatives were synthesized using N-methylindolyl acetic acid as a starting material. Sixteen new heterocyclics containing a pyrimidine ring were thus prepared. The pharmacological screening showed that many of these compounds have good analgesic and antiparkinsonian activities comparable to Voltarene^? and Benzatropine^? as reference drugs. The structure assignments of the new compounds based on chemical and spectroscopic evidence. The detailed synthesis, spectroscopic data, and pharmacological properties are reported.     

Synthesis,antioxidant and anticholinesterase activities of novel quinoline-aminophosphonate derivatives

A series of 20 novel α-aminophosphonate derivatives bearing quinoline or quinolone moiety was designed and synthesized via Kabachnik-Fields reaction in the presence of triethylammonium acetate as a solvent and catalyst under ultrasound irradiation. This procedure affords products in high yields and short reaction times. Molecular structures of the synthesized compounds 4a-g and 5a-m were confirmed using various spectroscopic methods. The antioxidant activity of these compounds was evaluated by eight complementary in vitro tests. The anticholinesterase activity (AChE, BChE) of these compounds were also evaluated. In addition, theoretical calculations of all compounds were investigated as corrosion inhibitors using density functional theory (DFT). The results revealed that 16 of these compounds exhibited high levels of antioxidant activities depending on the assay and that most compounds showed more potent inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).     

Synthesis,spectral characterization and antitumor activity of phenothiazine derivatives

Different types of phenothiazine derivatives were synthesized by reactions of 10-alkyl-10H-phenothiazine-3-carbaldehydes. Structures of the prepared compounds were confirmed through spectroscopic techniques such as IR, ¹H NMR, ¹³C NMR and mass spectroscopy. All the compounds were studied for their antitumor activities.     

Microwave-assisted synthesis,characterization and biological activity of novel pyrazole derivatives

A series of 1-(4-substitutedphenyl)-3-phenyl-1H-pyrazole-4-carbaldehydes 4a–l have been synthesized and tested for their biological activities. Formation of the pyrazole derivatives was achieved by treating with Vilsmeier-Haack reagent. The newly synthesized compounds were evaluated for their anti-inflammatory and analgesic activities compared to Diclofenac sodium as standard drug. Compounds 4g, 4i and 4k exhibited the maximum anti-inflammatory and analgesic activities. The detailed synthesis, spectroscopic and toxicity data are reported.     

A study on synthesis and antimicrobial activity of 4-acyl-pyrazoles

4-Acyl-pyrazole-3-carboxylic acids (1) were synthesized via the reaction of 4-acyl-2,3-furandiones (F) with hydrazone (1-benzylidene-2-(2,5-dimethyl-phenyl)-hydrazine) by heating under solid phase and their acid chlorides (2) were obtained. Then these derivatives were easily converted into the corresponding derivatives such as ester, amide, ureide, pyrazolo-pyridazine, etc. Totally 62 new compounds were synthesized. The structures of these new synthesized compounds were determined by spectroscopic methods and the in vitro antibacterial activity of newly synthesized compounds were carried out against some gram-positive and gram-negative bacteria by well diffusion method (zone inhibition). Our results have showed that these new synthesized compounds have much potent of antibacterial activity owing to containing of pyrazole and/or pyridazine, chromone, oxazine, furane, and pyrrole rings. Some of the new pyrazole derivatives exhibited higher activities than reference drugs against the representative bacteria.     

Synthesis, antibacterial and antifungal activity of some derivatives of 2-phenyl-chromen-4-one

Some derivatives of 2-phenyl-chromen-4-one (flavone ring) have been synthesized and tested for antibacterial and antifungal activities along with their chalcone precursors against four human pathogenic bacteria and five plant mould fungi. The structures of the synthesized compounds were elucidated by UV, IR and¹H NMR spectroscopic techniques, and elemental analysis. The antibacterial and antifungal screens of the synthesized compounds were performed in vitro by the filter paper disc diffusion method and the poisoned food technique.     

Synthesis of some novel thiocyanotopurine derivatives and investigation of their antimicrobial activity and DNA interactions

A series of 6-thiocyanatopurine derivatives introduced with different alkyl groups in position 9 was synthesized. The structures of the synthesized compounds were evaluated via spectroscopic methods and elemental methods of analyses. All the synthesized compounds were screened for their antibacterial activities against Gram-positive and Gram-negative bacteria and for their antifungal activities against yeast strains. All the synthesized compounds showed better antibacterial activities against Gram-positive bacteria compared to Gram-negative bacteria. DNA interactions with pBR322 DNA were determined. Most of the compounds caused conformational changes in DNA.     

Synthesis and biological activity of substituted 3-fluoro/3-trifluoromethyl 10H-phenothiazines, its ribofuranosides and sulfones

The present article describes the synthesis of new fluorinated 10H-phenothiazines by Smiles rearrangement. The reaction of these synthesized phenothiazines with sugar (beta-d-ribofuranose 1-acetate-2,3,5-tribenzoate) afforded the new ribofuranosides and the oxidation of these synthesized phenothiazines with 30% hydrogen peroxide in glacial acetic acid resulted in the formation of 10H-phenothiazine sulfones. These compounds were evaluated for their antioxidant and antimicrobial activities (using broth microdilution method). The structural assignments of the synthesized compounds were made on the basis of elemental analysis and spectroscopic data.     

Synthesis,characterization and antitumor activities of some novel thiazinones and thiosemicarbazones derivatives

Abstract

Two series of thiazinone and thiosemicarbazone derivatives (1-12) were synthesized using 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones (ABNs) and 3–alkyl–2,6–diarylpiperidin–4–ones as the starting materials. The structures of newly synthesized compounds were established on the basis of FT–IR, NMR spectroscopy and mass spectrometry. From the spectroscopic data, we identified that the cyclization reaction of thioamide with dialkyl acetylenedicarboxylate selectively gives six membered methyl 2-(2-(2,4-disubstituted-3-azabicyclo[3.3.1]nonan-9-ylidene)hydrazinyl)-4-oxo-4H-1,3-thiazine-6-carboxylates (1-6). In order to investigate the antitumor activities of the synthesized compounds, in vitro cytotoxicity studies were carried out using human prostate cancer cell lines. Tested compounds showed good/moderate activities against cancer cell lines and further investigation carried out by live/dead assay.     

Novel amino- and thio(substituted)-1,4-naphthoquinone (NQ) compounds: Synthesis and characterization

Abstract

Synthesis of new 1,4-naphthoquinone derivatives is important in terms of searching new biologically active substances. In particular, compounds with piperazine and thiol moiety in their structure, show a wide range of pharmacological activity such as anti-inflammatory, anticancer, anti-fungal, anti-bacterial, anti-allergic, apoptosis and radical scavenging activities. In this study, new amino- and thio(substituted) naphthoquinone derivatives were synthesized by the reaction of thiols and thioalcohols with four naphthoquinone compounds which were used as starting materials. The new compounds were purified by column chromatography. The structure of the compounds was confirmed by different spectroscopic techniques.     

Synthesis and Biological Evaluation of 2‐substituted‐6‐(morpholinyl/piperidinyl)pyridazin‐3(2H)‐ones as Potent and Safer Anti‐inflammatory and Analgesic Agents

A series of 2‐substituted‐6‐(morpholinyl/piperidinyl)pyridazin‐3(2H )‐ones was synthesized and the structures were established using various spectroscopic techniques. The target compounds were screened for anti‐inflammatory and analgesic activities at 20 and 40 mg/kg. The safety of the synthesized derivatives was evaluated by assessing anti‐platelet activity and ulcer index. The obtained pharmacological data revealed that 6‐morpholinyl derivatives 4a–12a were found to be somewhat more potent than 6‐piperidinyl derivatives 4b–6b. The 6‐morpholinyl substituted pyridazinone 12a exhibited maximum anti‐inflammatory and analgesic activities. Homoveratrylamine substituted compounds 6a and 6b emerged as promising leads in both the series with good anti‐inflammatory and analgesic activities without any ulcerogenicity. Anti‐platelet activity results of the compounds of both the series showed significantly low bleeding time in comparison with standard drug aspirin indicating the cardiovascular safety of new pyridazinones.     

Theoretical molecular predictions and antimicrobial activities of newly synthesized molecular hybrids of norfloxacin and ciprofloxacin

Antibiotics such as norfloxacin and ciprofloxacin are used to treat numerous bacterial infections. The present research work involves the molecular prediction, synthesis, characterization and in vitro antimicrobial activities of molecular hybrids of norfloxacin and ciprofloxacin. First set of compounds involve the substitutions of various amines at third position of ciprofloxacin and norfloxacin. On the other hand, second set of molecular hybrids include the substitution of different amines at seventh position along with linker (─COCH₂─). These synthesized compounds were identified by TLC technique and well characterized by various spectroscopic techniques such as IR, NMR, and ESI-MS. Molecular prediction of these newly synthesized compounds have been carried out using the SwissADME, ADMETLab software. Their cytotoxicity parameters have also been studied using Osiris software. It was observed that almost all these molecular hybrids suitable for their drug likeness properties. Further, these newly synthesized compounds were subjected to study their antimicrobial activities in vitro. The third substituted as well as most of seventh substituted molecular hybrids have shown 10-folds increase in their antibacterial activity as compared to the standard drug ciprofloxacin. Some of these compounds have also shown their potency when subjected to study their cytotoxicity test against Escherichia coli AB 1157, proficient to prepare damage in DNA.     

Some divalent metal(II) complexes of novel potentially tetradentate Schiff base N,N′‐bis(2‐carboxyphenylimine)‐2,5‐thiophenedicarboxaldhyde: Synthesis,spectroscopic characterization and bioactivities

A novel tetradentate dianionic Schiff base ligand, N ,N ′‐bis(2‐carboxyphenylimine)‐2,5‐thiophenedicarboxaldhyde (H₂L) and some first row d‐transition metal chelates (Co(II), Cu(II), Ni(II) and Zn(II)) were synthesized and characterized using various physicochemical and spectroscopic methods. The spectroscopic data suggested that the parent Schiff base ligand coordinates through both deprotonated carboxylic oxygen and imine nitrogen atoms. The free Schiff base and its metal chelates were screened for their antimicrobial activities for various pathogenic bacteria and fungi using the agar well diffusion method. The antibacterial and antifungal activities of all the newly synthesized compounds are significant compared to the standard drugs ciprofloxacin and nystatin. The antioxidant activities of the compounds were determined by reduction of 1,1‐diphenyl‐2‐picrylhydrazyl and compared with that of vitamin C as a standard. DNA binding ability of the novel Schiff base and its complexes was investigated using absorption spectroscopy, fluorescence spectroscopy, viscosity measurements and thermal denaturation. The obtained results clearly demonstrate that the binding affinity with calf thymus DNA follows the order: Cu(II) complex > Ni(II) complex > Zn(II) complex > Co(II) complex >H₂L. Furthermore, the DNA cleavage activity of the newly synthesized ligand and its metal complexes was investigated using supercoiled plasmid DNA (pUC18) gel electrophoresis.     

Bis benzothiophene Schiff bases: synthesis and in silico-guided biological activity studies

Since benzo [ b ] thiophene scaffold is one of the privileged structures in drug discovery as this core exhibitsactivities for different biological problems, in this study bis (benzo[ b ]thiophene-2-yl) alkyl methanimine derivatives (1-9) were synthesized by reacting benzo[ b ]thiophene-2-carbaldehyde with diamines. All newly compounds were characterized by IR, ¹H NMR and ¹³C NMR spectroscopic methods. Synthesized compounds were investigated using binary QSARbased models on therapeutic activity prediction of synthesized compounds and they showed high predicted activities in following diseases: bacterial, angina, allergy, depression and obesity. Thus, they were then tested for their antimicrobial and antileishmanial activities as a result of this theoretical study. Compound 1(N, N’- (propane-1,3-diyl) bis (1-(benzo [ b ] thiophene-2-yl)) methanimine) was found the most active compound in both diseases. Thus, its molecular docking studies were also carried out.     

An efficient one pot I2/DMSO mediated synthesis and molecular modeling of novel fused pyrimidine-chromone hybrids bearing potential antibacterial and antifungal pharmacophores sites

A series of novel ethyl-l, 1, 2, 3, 6-tetrahydro-4-methyl-1-(6-methyl-4-oxo-4H-chromene-2-yl)-2-oxo/thioxo-6-phenyl pyrimidine-5-carboxylate compounds ( 2a–2k ) were synthesized using I₂/DMSO as a competent and cost-effective catalyst in one pot green solvent system from corresponding chalcones ( 1a–1k ) in better yields. IR, ¹H-NMR, ¹³C-NMR, Mass, and X-ray diffraction spectroscopic techniques were used for the characterization of newly synthesized compounds. All the compounds were tested for in-vitro antibacterial activities against gram-positive and gram-negative bacteria like Staphylococcus aureus, Salmonella abony, Staphylococcus epidermidis, and Escherichia coli. Antifungal activities were also performed against Candida albicans and Aspergilus niger. It was found that the presence of electron withdrawing group on the aromatic ring attached to chromone ring increases the antibacterial activities ( 2g , 2h , and 2k ); while the presence of electron releasing groups decreases activities. The presence of electron donating groups (─OCH₃, ─Cl), on the phenyl ring attached to pyrimidine skeleton influenced negatively for the antibacterial activities.     

Synthesis of Some Substituted Pyrazolopyrimidine Derivatives: An Environmentally Benign Approach

Pyrazolopyrimidines constitute a medicinally important class of heterocyclic compounds. Herein, we report an efficient and environmentally benign method for the synthesis of pyrazolo[3,4‐d]pyrimidin‐3‐ones from 2,4‐dinitrophenylhydrazine and diethyl malonate under microwave irradiation in 1,3‐dibutylimidazolium bromide ionic liquid. The synthesized compounds were analyzed by elemental analysis and standard spectroscopic techniques. The compounds were screened for their antibacterial and antifungal activities.     

Synthesis of new bis(thiosemicarbazone) derivatives and DFT analysis of antioxidant characteristics in relation to HAT and SET reactions

A series of new bis(thiosemicarbazones) have been synthesized from terephthalaldehyde and various thiosemicarbazides. IR, ¹H NMR, ¹³C NMR spectroscopic methods, and elemental analysis were used to characterize the identification of the synthesized compounds. The in vitro antioxidant activity determinations were made using the 1,1-Diphenyl-2-Picryl Hydrazil (DPPH) method. The compounds exhibited very different inhibition activities with the change of groups attached to the bis(thiosemicarbazone) structure. The spectral and electronic properties of the compounds were investigated by DFT calculation. Intramolecular interactions were analyzed by QTAIM and IRI calculations. Intrinsic bond strength index values of the N–H bonds, Fukui indices and the local electron affinities of the compounds were calculated, and the relationships between the compounds and their antioxidant activity properties were investigated. The SET and HAT mechanisms in the reactions of the compounds with DPPH were affected by the concentration of the compounds, and the possible effects of the parameters supporting the dominant characteristics in these reactions were examined using theoretical data.     

The cytotoxic activities of imidazole derivatives prepared from various guanylhydrazone and phenylglyoxal monohydrate

Abstract

A series of imidazole derivatives were synthesized from two-component condensation reaction of phenylgloxal monohydrate with guanylhydrazone. They were characterized by spectroscopic and analytical techniques. The in vitro anticancer evaluation of these compounds was done on human breast cancer (MCF-7) and human liver cancer (HepG2) cell lines using the MTT assay method. Most of the newly synthesized compounds displayed cytotoxic activity against these cancerous cells. In fact, compounds 3a, 3e, and 3?h exhibited more cytotoxic activities than the positive control drugs, fluro-5, and irinocam, against the MCF-7 cell line. Almost all the compounds, except for three, 3b, 3d, and 3f, gave more cytotoxic results than cisplatin. Therefore, these compounds could be considered for further development as anticancer drug candidates.