Synthesis,SAR Study and Evaluation of Mannich and Schiff Bases of Pyrazol-5(4H)-one Moiety Containing 3-(Hydrazinyl)-2-phenylquinazolin-4(3H)-one

In the present investigation, a series of 12 Mannich bases (QP1-12) and 5 Schiff bases (QSP1-5) of pyrazol-5(4H)-one moiety containing 3-(hydrazinyl)-2-phenylquinazolin-4(3H)-one has been synthesized and characterized by physicochemical as well as spectral means. The synthesized Mannich and Schiff bases were screened for their preliminary antimicrobial activity against Gram-positive and Gram-negative bacterial as well as fungal strains by the determination of zone of inhibition. Mannich bases (QP1-12) were found to be more potent antibacterial agents against Gram-positive bacteria, whereas Schiff bases (QSP1-5) were more potent against Gram-negative bacteria and fungi. Minimum inhibitory concentration result demonstrated that Mannich base compound (QP7) having ortho -OH and para -COOH group showed some improvement in antibacterial activity (minimum inhibitory concentration of 48.88×10⁻³ μM/ml) among the tested Gram-positive organisms and it also exhibit minimum inhibitory concentration of value of 12.22×10⁻³ μM/ml for Klebsiella pneumoniae. The antitubercular activity of synthesized compounds against Mycobacterium tuberculosis (H₃₇Rv) was determined using microplate alamar blue assay. Compound QP11 showed appreciable antitubercular activity (minimum inhibitory concentration of 6.49×10⁻³ μM/ml) which was more active than the standard drugs, ethambutol (minimum inhibitory concentration of 7.60×10⁻³ μM/ml) and ciprofloxacin (9.4×10⁻³ μM/ml). Compounds QP11, QP9, QSP1, QSP2, and QSP5 have good selective index and may be selected as a lead compound for the development of novel antitubercular agents.     

Synthesis, spectroscopic, thermal and antimicrobial studies of Co(II), Ni(II), Cu(II) and Zn(II) complexes with Schiff base derived from 4-amino-3-mercapto-6-methyl-5-oxo-1,2,4-triazine

Coordination complexes of Co(II), Ni(II), Cu(II) and Zn(II) with Schiff base derived from syringaldehyde and 4-amino-3-mercapto-6-methyl-5-oxo-1,2,4-triazine have been synthesized. These complexes have been characterized by elemental analysis, magnetic moment, spectroscopic (IR, Electronic, ¹H NMR, ESR) and thermogravimetric analysis. Magnetic and spectral data suggest octahedral geometry for Co(II), Ni(II) and Zn(II) complexes and square planar for Cu(II) complexes. The presence of coordinated water in metal complexes was confirmed by thermal and IR data. The Schiff base and its metal complexes have been screened for antibacterial (Pseudomonas aeruginosa, Bacillus subtilis, Escherichia coli, Staphylococcus aureus) and antifungal activities (Aspergillus niger, A. flavus). A comparison is made between activities of complexes with Schiff base and with the standard antibiotics.     

Synthesis and pharmacological evaluation of novel 1-(piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one derivatives as potential antimicrobial agents

Novel compounds of biological interest were synthesized by in situ reduction of Schiff’s base of 5,6-dimethoxy indanone and 1-(piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one in the presence of Ti(OiPr)₄ and NaBH₃CN. Further alkylation using different alkyl/aryl halides in the presence of NaH in DMF gave a series of novel compounds. A formation of newly synthesized compounds was confirmed on the basis of their spectral and elemental analysis. Further these compounds were screened for their antimicrobial activity and found to have promising antibacterial and antifungal activity.     

Synthesis and biological evaluation of 1-(3-chloro-2-oxo-4-phenylazetidin-1-yl)-3-(2-oxo-2-(10H-phenothiazin-10-yl)ethyl)urea derivatives

A new series of eleven novel 1-(3-chloro-2-oxo-4-phenylazetidin-1yl)-3-(2-oxo-2-(10H-phenothiazin-10-yl)ethyl)urea derivatives were synthesized by cyclocondensation of various Schiff bases of phenothiazine with chloroacetyl chloride in the presence of triethylamine. Various Schiff bases of phenothiazine were synthesized by condensation of 4-(2-oxo-2-(10H-phenothiazin-10-yl)ethyl semicarbazide with various aryl aldehydes. The synthesized compounds were characterized by IR, MASS and ¹H NMR spectral data and evaluated for in vitro antimicrobial, antitubercular, antioxidant and anticancer activities by disc diffusion method, MIC method, REMA, DPPH, FRAP and MTT assay method, respectively. All synthesized compounds showed moderate-to-significant anti-bacterial and anti-fungal activity and compound 4d, 4g, 4h and 4k showed good antioxidant activity with EC₅₀ value of 55, 57, 56 and 47 μg/ml tested by DPPH method. The compounds 4j at a concentration of 10 μg/ml showed inhibition against the growth of Mycobacterium tuberculosis and 4f showed significant activity against human cervical cancer cell line with IC₅₀ values of 18.26 μM.     

Synthesis of 3-{4-[4-dimethylamino-6-(4-methyl-2-oxo-2H-chromen-7-yloxy)-[1,3,5]triazin-2-ylamino]-phenyl}-2-phenyl-5-(4-pyridin-2-yl-piperazin-1-ylmethyl)-thiazolidin-4-one and their biological evaluation

A novel series of thiazolidinone derivatives namely 3-{4-[4-dimethylamino-6-(4-methyl-2-oxo-2H-chromen-7-yloxy)-[1,3,5]triazin-2-ylamino]-phenyl}-2-phenyl-5-(4-pyridin-2-yl-piperazin-1-ylmethyl)-thiazolidin-4-one have been synthesized from the intermediate 7-[4-(4-amino-phenylamino)-6-dimethylamino-[1,3,5]triazin-2-yloxy]-4-methyl-chromen-2-one (7). Condensation reaction of compound 7 with different aldehyde derivatives were performed to give Schiff base derivatives, which after cyclization gave thiazolidinones and they were incorporated with 1-pyridin-2-yl-piperazine to get target compounds. The newly synthesized compounds were evaluated for their antimicrobial activity against eight bacteria (S. aureus, B. cereus, E. coli, P. aeruginosa, K. pneumoniae, S. typhi, P. vulgaris, and S. flexneria) and four fungi (A. niger, C. albicans, A. fumigatus, and A. clavatus).     

Synthesis characterization and biological evaluation of some alkoxyphthalimide derivatives of 3-(4-substituted phenyl)-6,6-diphenyl-3,3a-dihydro-2H-imidazo[2,1-b]pyrazolo[3,4-d][1,3]thiazol-7(6H)-one

A series of 2-N-ethoxyphthalimido 3-(4-substitutedphenyl)-6,6-diphenyl-3,3a-dihydro-2H-imidazo[2,1-b]pyrazolo[3,4-d][1,3]thiazol-7(6H)-one(7a–e) and 4-(4-substituted phenyl)-2-(N-ethoxyphthalimido amino)-7,7-diphenylimidazo[2′,1′:2,3][1,3]thiazolo[4,5-d] pyrimidin-8(7H)-one (9a–e) have been designed and synthesized starting from thiohydentoin (1). The structure of all synthesized compounds has been established by IR, ¹H NMR, ¹³C NMR and mass studies. These compounds have been screened for antimicrobial activities in order to evaluate the possibility of the derivatives to be used as potential chemotherapeutic agents.     

Antibacterial and antifungal oxovanadium(IV) complexes of triazole-derived Schiff bases

A newly synthesised series of antibacterial and antifungal triazole-derived Schiff base ligands (L ¹ )–(L ⁵ ) has been prepared by the condensation reaction of 3,5-diamino-1,2,4-triazole with methyl-, chloro- and nitro-substituted thiophene-2-carboxaldehydes in (1:2) molar ratio. The most probable structures of the synthesised Schiff base ligands were established on the basis of their physical, spectral (IR, ¹H and ¹³C NMR and mass spectrometry) and analytical (CHN analysis) data. These Schiff bases potentially act as bidentate ligand and were further made to react with the vanadyl(IV) sulphate (VOSO₄·5H₂O) in (1:2) (metal:ligand) molar ratio to prepare their oxovanadium(IV) complexes (1)–(5). All oxovanadium(IV) complexes showed a square-pyramidal geometry which was established on the basis of their physical, spectral and analytical data. The Schiff base ligands and their vanadyl(IV) complexes have been screened for their in vitro antibacterial, antifungal and brine shrimp bioassay. The antimicrobial activity data showed the vanadyl(IV) complexes to be more potent antibacterial and antifungal than the parent Schiff bases against one or more bacterial and fungal species.     

9-(2-膦酰甲氧乙基)腺嘌呤及其位置异构体3-(2-膦酰甲氧乙基)腺嘌呤的合成和抗病毒活性研究

Phosphonylmethoxyethyl)adenine (1),PMEA,an acyclic nucleotide withbroad-spectrum antiviral activity was synthesized with some modifications of Holy's procedure.Simutaneously,an N-3 regioisomer(2)of PMEA and a by-preduct, formaldehyde di-[2-(9-adenyl)ethyl] acetal(7)were seperated by silica gel chromatography in the ratio of 50:10:1.Compound(2)and(7) are new compounds that we have not yet found in literatures. The structure of them weredetermined with ¹HNMR,2DNMR, MS and Spot test.Antiviral test showed that N-3 isomer(2)completely lost activity against both HIV-1 and HSV-1 in vitro. It seems that regiospecificity of theacyclic nucleotide structure is important for antiviral activity.     

Synthesis and antimicrobial screening of 5-(benzylidene)-3-phenylthiazolidin-4-one derivatives incorporating thiazole ring

The present article deals with the synthesis and antimicrobial screening of a series of N-(5-(2-(5-(arylidene)-4-oxo-3-phenylthiazolidin-2-ylidene)hydrazinecarbonyl)-4-methylthiazol-2-yl)-4-methoxybenzamides (6a–o). The structures of these compounds have been elucidated by spectra (IR, ¹H NMR, ¹³C NMR, mass spectra). All the synthesized compounds were screened for in vitro antibacterial activity against Gram-positive (Staphylococcus aureus, Streptococcus pyogenes) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria. These compounds were also tested for their inhibitory action against three strains of fungi (Candida albicans, Aspergillus niger, Aspergillus clavatus). The thiazole derivatives discovered in this study may provide valuable therapeutic intervention for the treatment of microbial diseases, especially against bacterial and fungal infections.     

Schiff bases in medicinal chemistry: a patent review (2010-2015)

Introduction: Schiff bases are synthetically accessible and structurally diverse compounds, typically obtained by facile condensation between an aldehyde, or a ketone with primary amines. Schiff bases contain an azomethine (-C = N-) linkage that stitches together two or more biologically active aromatic/heterocyclic scaffolds to form various molecular hybrids with interesting biological properties. Schiff bases are versatile metal complexing agents and have been known to coordinate all metals to form stable metal complexes with vast therapeutic applications.

Areas covered: This review aims to provide a comprehensive overview of the various patented therapeutic applications of Schiff bases and their metal complexes from 2010 to 2015.

Expert opinion: Schiff bases are a popular class of compounds with interesting biological properties. Schiff bases are also versatile metal complexing ligands and have been used to coordinate almost all d-block metals as well as lanthanides. Therapeutically, Schiff bases and their metal complexes have been reported to exhibit a wide range of biological activities such as antibacterial including antimycobacterial, antifungal, antiviral, antimalarial, antiinflammatory, antioxidant, pesticidal, cytotoxic, enzyme inhibitory, and anticancer including DNA damage.     

Synthesis,characterization and biological applications of novel Schiff bases of 2-(trifluoromethoxy) aniline

A series of five new Schiff bases (1–5) were synthesized by reacting 2-(trifluoromethoxy) aniline with different aromatic aldehydes. The Schiff base compounds were characterized by spectroscopic and analytical methods. Crystal structure of one new compound was also reported. The pharmacological properties, including antibacterial (14 bacterial species), antifungal (7 strains),antimalarial, anti-trypanosomal and anti-HIV activities of the compounds, were investigated. Cytotoxicity of the tested compounds was evaluated against human cervix adernocarcinoma cells (HeLa). Bacterial minimum inhibitory concentration (MIC) results by broth microdilution method showed that Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Proteus vulgaris, Klebsiella oxytoc and Klebsiella pneumonia were more sensitive in the presence of tested compounds with an MIC value of 15.6 µg/mL. All the tested compounds showed good to moderate activity against fungi. The sensitivity of Aspergillus fumigatus was higher than other strains with aminimum cell death concentration (MFC) of 15.6 µg/mL. Compound 1 showed greater antimalarial and anti-trypanosomal properties with very low to no cytotoxic effects against HeLa cells as compared with compound 5, while other compounds exhibited poor activity. Compounds 1–5 demonstrated good activity against HIV type-1. These Schiff base compounds could be used as good antimicrobial agents.     

Synthesis, characterization, antibiogram and DNA binding studies of novel Co(II), Ni(II), Cu(II), and Zn(II) complexes of Schiff base ligands with quinoline core

A series of Co(II), Ni(II), Cu(II), and Zn(II) complexes of Schiff base ligands L¹H₃ and L²H have been prepared. The ligands are synthesized by the condensation of 2-hydroxy-3-formylquinoline with salicyloylhydrazide and 2-hydrazinobenzothiazole in absolute ethanol. The prepared complexes were characterized by the analytical and spectral techniques. The stoichiometry of the complexes is found to be 1:1. The presence of coordinated and lattice water is confirmed by the TG and DTA studies. Subsequently all the prepared complexes were screened for antimicrobial activity against bacteria and fungi. The Cu(II) complexes have been found to be more active than the ligand. In addition the DNA binding/cleaving capacity of the compounds was analyzed by absorption spectroscopy, viscosity measurement, thermal denaturation, and gel electrophoresis methods.     

Design, synthesis, molecular modeling, and biological evaluation of sulfanilamide-imines derivatives as potential anticancer agents

A series of sulfanilamide Schiff base derivatives (1 to 15) have been designed as potential antitubulin agents depending on the chemical structures of combretastatine A-4 and isoquinoline sulfamate (antimitotic agents under investigation). The designed compounds were synthesized by microwave chemical synthesis, their purity was confirmed by melting point and HPLC and chemical structures were determined by FT-IR, UV, and ¹H and ¹³C-NMR spectroscopic techniques. The synthesized compounds have been docked in the colchicine binding site of β-tubulin using molecular modeling programs and the antitumor activities were screened on human breast and lung cancer cells by cell counting assay. Some tested compounds showed potent and selective activity against breast cancer (MCF-7) with IC₅₀ range of 90 to 166 μM. With regarding broad-spectrum activity, compounds 4, 8, and 13 have shown potent antitumor activity against human breast and human lung cells with IC₅₀ range of 96 to 140 μM. The obtained results suggest that the sulfanilamide Schiff base derivatives might potentially constitute an interesting novel class of anticancer agents, which deserve further studies.     

Synthesis and evaluation of meta substituted 1-(aryloxypropyl)-4-(chloroaryl) piperazines as potential atypical antipsychotics

A series of 1-(aryloxypropyl)-4-(chloroaryl) piperazines have been synthesized based upon their physicochemical similarity with respect to standard atypical antipsychotic drugs and their potential to cross the blood–brain barrier (log BB) as calculated by appropriate software programmes. The target compounds were evaluated for atypical antipsychotic activity in apomorphine-induced mesh climbing and stereotypy assays in mice. The compounds 8, 9 and 10 bearing hydrogen bond acceptor substituents have emerged as important lead compounds showing higher efficacy along with potential atypical antipsychotic profile.     

Investigation of myorelaxant activity of 9-aryl-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-diones in isolated rabbit gastric fundus

In this study, twelve compounds having 9-aryl-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-dione structure were synthesized by reaction of 5-methyl-1,3-cyclohexanedione, the appropriate aromatic aldehydes, and ammonium acetate in methanol. The structures of the compounds were elucidated by infrared, ¹H- and ¹³C-nuclear magnetic resonance spectroscopy (-NMR), mass spectroscopy, and elemental analysis. The maximum relaxant effects (E _max) and pD2 values of the compounds 3a–l and pinacidil were tested on isolated strips of rabbit gastric fundus smooth muscle.     

3-(4-Amidinophenyl)-brenztraubensäure analoge 5-Amidinobenzylbarbitursäuren

5-(Amidinobenzyl)barbituric Acids that are Analogous to 3-(4-Amidinophenyl)pyruvic Acid Six title compounds have been synthezised and tested for antithrombin activity and their influence on other blood clotting parameters. In concentrations up to 5·10^?4 mol·1^?1 no effect was observed.     

Synthesis of 5-(n-isopropylthiocarbamoyl)-spinaceamines: Analogs of antisecretory and antiulcer derivatives of spinaceamine

A series of 5-(N-isopropylthiocarbamoyl) derivatives of spinaceamine and spinacine have been synthesized for pharmacological testing. N-Phenacylium salts were obtained via the interaction of 1-and 1,2-substituted imidazo[4,5-c]pyridines with p-methoxyphenacyl bromide. The reduction of N-phenacylium salts with sodium borohydride in alcohol leads to the formation of 5-(β-hydroxy-β-p-methoxyphenetyl)spinaceamines, and subsequent boiling with concentrated hydrochloric acid leads to cleavage of the terminal C-N⁵ bonds with the formation of 1-substituted and 1,2-disubstituted spinaceamines. Final treatment with isopropylisothiocyanate converts these intermediate compounds into the target 5-(N-isopropylthiocarbamoyl) derivatives. Lithium and potassium salts of spinacine were reacted with isopropylisothiocyanate to obtain the corresponding thioureas, which were converted into hydrochlorides by treatment with hydrogen chloride saturated ether. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 2, pp. 5–9, February, 2006.     

Synthesis and Characterization of Cr(III), Mn(III), Fe(III), VO(IV), Zr(IV) and UO2(VI) Complexes of Schiff Base Derived from Isonicotinoyl Hydrazone

2-hydroxy-5-chloro-3-nitroacetophenone isonicotinoyl hydrazone as a Schiff base ligand and its complexes with Cr(III), Mn(III), Fe(III), VO(IV), Zr(IV) and UO₂(VI) metal ions have been synthesized. The ligands as well as their metal complexes were well characterized using various physicochemical techniques such as elemental analyses, molar conductance measurements, magnetic measurements, thermal analysis, electronic and IR spectral studies. On the basis of these studies, square pyramidal stereochemistry for Mn(III) and VO(IV) complexes while octahedral stereochemistry for all the other complexes have been suggested. The complexes were found to be stable up to 60-70° and thermal decomposition of the complexes ended with respective metal oxide as a final product. The thermal data have been analyzed for kinetic parameters using Broido and Horowitz-Metzger methods. The synthesized Schiff base ligand and its complexes were also tested for their antimicrobial activity using various microorganisms.     

Synthesis and in vitro antileukemic activity of some new 1,3-(oxytetraethylenoxy)cyclotriphosphazene derivatives

A new series of 1,3-(oxytetraethylenoxy)cyclotriphosphazene derivatives bearing 2-chloroethylamine or salicylaldehyde (2-hydroxybenzaldehyde) or its Schiff base (after condensation with 2-chloroethylamine) units and having also 2-naphthyl or anthraquinone groups as cosubstituents has been synthesized. The in vitro cytotoxic activity of these compounds against a panel of four cancer cell lines has been studied. Most of the compounds exhibited antiproliferative activity in the range of the international criterion for synthetic agents (4 microg/mL) against the MOLT4, L 1210, HL-60, and P388 cell lines chosen for testing.     

Synthesis, characterization, and antibacterial activity of a novel heterocyclic Schiff’s base and its metal complexes of first transition series

The synthesis of a series of some novel Schiff base complexes of Cu(II), Ni(II), Co(II), Mn(II), Zn(II) with a tetradentate Schiff base has been achieved by the reaction of malonyl hydrazide with dehydroacetic acid in ethanol under refluxing condition. All the synthesized metal complexes and ligand were characterized on the basis of elemental analysis, UV–Visible, ¹H and ¹³C NMR, IR spectroscopy and mass spectrometry. The IR spectral data suggest that azomethine N and enolic O atom are involved in coordination with metal ions, and the ligand behaves as a tetradentate ligand with ONNO donor atoms. The mass spectrum of the complexes reveals the formation of metal ligand bonding in stoichiometric ratio 1:1 (M:L). The UV–Visible data suggest the square planner geometry for the synthesized complexes. All compounds were screened for their antibacterial activity against gram-positive and gram-negative bacteria using Ampicillin as a standard drug. It has been found that metal complexes show enhanced activity as compared to ligand, and some modification in ligand structure may lead to better antibacterial agents in future.