Synthesis,characterization, and antioxidant and anticholinesterase activities of pyrazolo derivatives

Twenty-four pyrazolo derivatives (1–4)(a-f) were synthesized and characterized by FTIR, ¹H, and ¹³C NMR (Nuclear Magnetic Resonance), and elemental analysis. The synthesized compounds were also investigated for their antioxidant and anticholinesterase activities. The compounds (3–4)(a-f) carrying morpholine ring were more active than the piperidinyl containing compounds (1–2)(a-f) in both activities. The compound 4f showed higher activity in both assays as compared with the others. Additionally, the anticholinesterase activity test provided higher values than the galantamine in the BChE assay. Therefore, compound 4f can be used as anticholinesterase agent and/or anticholinesterase assay standard.     

Synthesis,antioxidant, and anticholinesterase activities of novel N-arylsulfonyl hydrazones bearing sulfonate ester scaffold

In this research, two new series of N-arylsulfonyl hydrazone compounds ( 14 – 25 ) possessing a sulfonate moiety were synthesized and characterized by elemental analysis and various spectroscopic techniques including fourier transform infrared (FT-IR), ¹H-, and ¹³C nuclear magnetic resonance (NMR). These compounds synthesized as target molecules ( 14 – 25 ) were tested for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition activities and antioxidant potential. The antioxidant capacities of the tested molecules were determined by four different assays. The IC₅₀ values of the screened molecules were determined in the range of 60.14 ± 0.25–84.81 ± 1.09 μM against AChE and in the range of 70.11 ± 0.67–93.60 ± 0.47 μM against BChE. In the AChE assay, 4-hydroxybenzaldehyde-based compound 25 (60.14 ± 0.25 μM) showed the highest activity in comparison to rivastigmine (501 ± 3.08 μM). This compound (71.42 ± 0.19 μM) is also one of the compounds with the highest activity against BChE. In the BChE assay, 2-hydroxybenzaldehyde-based compound 19 (70.11 ± 0.67 μM) indicated the highest activity in comparison to rivastigmine (19.95 ± 0.20 μM). In antioxidant activity studies, the tested molecules showed lower activities than the standard compounds (butylated hydroxytoluene and α-tocopherol). Consequently, some novel compounds can be used as potential inhibitor candidates in future studies.     

Synthesis and anticholinesterase activities of O-phosphorylated derivatives ofd-allylpseudoephedrine

An immunochemical investigation has been made of the culture liquid after the cultivation of ten strains of the microorganisms Yersinia pseudotuberculosis. It has been shown that in the process of vital activity all the strains investigated, to a greater or smaller degree, produce into the culture medium products of catabolic breakdown consisting of fragments of receptor proteins which are possibly, regulators of metabolic processes taking place under the influence of the constantly changing conditions of the growth medium.Pacific Ocean Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, Vladivostok. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 436–439, May–June, 1993.     

Synthesis and anticholinesterase activities of O-phosphorylated derivatives ofd-allylpseudoephedrine

The synthesis of O-phosphorylated derivatives of d-allylpseudoephedrine under the conditions of phase-transfer catalysis is described. The results of a study of their anticholinesterase properties are given.Institute of Organic Synthesis and Coal Chemistry, National Academy of Sciences, Republic of Kazakhstan, Karaganda. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 408–411, May–June, 1994.     

Synthesis and structure of gossypol bisdiethylaminophenylimines and their antioxidant and anticholinesterase activities

The synthesis has been performed of gossypol gis-p- and-m-diethylaminophenylimines, which possess anticholinesterase activity, antioxidant action on rat brain synaptosome membranes, and an innibiting influence on the oxidase system of zymosan-activated macrophages.A. S. Sadykov Institute of Bioorganic Chemistry, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 184–188, March–April, 1991.     

Synthesis,spectroscopic studies,and antioxidant activities of novel thio/carbohydrazones and bis-isatin derivatives from terephthalaldehyde

New bis(isatins-thio/carbohydrazones) based on Schiff bases were prepared from terephthalaldehyde biscarbohydrazone and 5-substituted isatins in the presence of a drop of sulfuric acid under reflux in ethanol. Terephthalaldehyde bis(thio/carbohydrazone) was synthesized by the reaction of (thio)/carbohydrazide and terephthalaldehyde in the presence of a few drops of acetic acid under reflux in ethanol. The structures of these synthesized compounds were determined using IR, ¹H NMR, and ¹³C NMR spectroscopy and elemental analysis. The in vitro antioxidant activity of all the compounds was determined by the 1,1-diphenyl-2-picryl hydrazyl (DPPH.) free radical scavenging method. Compound 2 showed the best antioxidant activity.     

Synthesis of novel 1,3,4-oxadiazole derivatives and their nucleoside analogs with antioxidant and antitumor activities

A series of new (1,3,4-oxadiazol-2-yl)-1H-benzo[h]quinolin-4-one derivatives were synthesized, including glucose and xylose hydrazones that were obtained by the reaction of hydrazides with monosaccharides. Cyclization of the sugar hydrazones with acetic anhydride afforded substituted oxadiazoline derivatives. The newly synthesized compounds were evaluated for their antioxidant properties and cytotoxicity, and showed moderate to high activities.     

Synthesis and anticholinesterase activities of quininyl dialkyl phosphates

The results are given of the synthesis of dialkyl phosphate derivatives of the alkaloid quinine and the study of their inhibitory activity in relation to the cholinesterases of various animal species. Institute of Organic Chemistry and Coal Chemistry, National Academy of Sciences, Republic of Kazakhstan, Karaganda. I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 411–414, May–June, 1994.     

Synthesis of a number of derivatives of alkaloids and of nitrogen-containing heterocycles and their anticholinesterase activities

N-Methyl- and N-phenylcarbamates based on a number of alkaloids and nitrogen-containing heterocycles have been synthesized, and they have proved to be weak irreversible inhibitors of acetylcholinesterase and butyrylcholinesterase. It has been shown that the choline fragments of the above-mentioned carbamates and their β-methylcholine analogs are reversible inhibitors of both cholinesterases and make a substantial contribution to the anticholinesterase activity. Selective inhibitors of ACE and BuCE have been found among the compounds synthesized.     

Cytotoxicity, antioxidant, and antimicrobial activities of novel 2-quinolone derivatives derived from coumarin

Coumarins are important and useful compounds with diverse pharmacological properties. New coumarin derivatives namely N-aminoquinoline-2-one 1, 1-((4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)methyleneamino)quinolin-2(1H)-one 2 and 1,1′-(1E,1′E)-(1,4-phenylenebis(methan-1-yl-1-ylidene))bis(azan-1-yl-1-ylidene)diquinolin-2(1H)-one 3, were synthesized and characterized by UV–Vis, FT-IR, and NMR spectra in addition of elemental analysis. The synthesized compounds (2 and 3) show considerable anticancer activity against HEp-2 cell line. Synthesized compounds (2 and 3) were tested against selected types of microbial organisms and showed significant activities. The free-radical scavenging activity of synthesized compounds (2 and 3) have been determined by their interaction with the stable free-radical 1,1-diphenyl-2-picrilhydrazyl (DPPH) and all the compounds have shown encouraging antioxidant activities.     

Synthesis of a number of derivatives of alkaloids and of nitrogen-containing heterocycles and their anticholinesterase activities

N-Methyl- and N-phenylcarbamates based on a number of alkaloids and nitrogen-containing heterocycles have been synthesized, and they have proved to be weak irreversible inhibitors of acetylcholinesterase and butyrylcholinesterase. It has been shown that the choline fragments of the above-mentioned carbamates and their -methylcholine analogs are reversible inhibitors of both cholinesterases and make a substantial contribution to the anticholinesterase activity. Selective inhibitors of ACE and BuCE have been found among the compounds synthesized.A. S. Sadykov Institute of Bioorganic Chemistry, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodynkh Soedinenii, No. 6, pp. 825–831, November–December, 1988.     

Expeditious synthesis,antileishmanial and antioxidant activities of novel 3-substituted-4-hydroxycoumarin derivatives

A series of novel 3-substituted-4-hydroxycoumarin derivatives 6(a–1) were synthesized in high yield using one-pot three component coupling reaction catalyzed by ceric ammonium nitrate. These compounds were evaluated for antileishmanial activity against Leishmania donovani promastigotes and antioxidant activity(DPPH-radical scavenging activity). Two compounds, 6h(IC_(50)= 9.90 μmol/L) and 6i(IC_(50)= 6.90 μmol/L) displayed potent antileishmanial activity when compared with standard antileishmanial agents pentamidine(IC_(50)= 16.15 μmol/L) and miltefosine(IC_(50)= 12.50 μmol/L). Three compounds, 6c(IC_(50)= 10.79 μmol/L), 6h(IC50= 10.60 μmol/L), and 6i(IC_(50)= 10.73 μmol/L) showed significant antioxidant activity favorably with the antioxidant standards butylated hydroxy toluene(IC_(50)= 16.47 μmol/L) and ascorbic acid(IC_(50)= 12.69 μmol/L). A molecular docking study of compounds 6(a–1) suggested a possible mode of binding with the Adenine phosphoribosyltransferase enzyme of L.donovani. ADME properties were predicted in silico and support the potential of 6(a–1) to show favorable drug-like properties.     

Synthesis and insecticidal activities of novel derivatives of podophyllotoxin

In order to find the biorational pesticides, eight novel 4beta-substituted phenoxyaniline derivatives of podophyllotoxin (4a-h) have been synthesized with significant stereoselectivity and improved yields by employing the BF(3).Et(2)O/NaI reagent system and evaluated for insecticidal activity against Pieris rapae as well as for their antifeedant effect against fifth instar larvae of P. rapae. The results showed that all these derivatives of PPT showed delayed insecticidal activity, which is different from the traditional neurotoxic insecticides. Among them, compounds possessing a 4beta-phenoxyaniline moiety substituted at para (CO(2)C(2)H(5), Cl, and OH) position exhibited greater insecticidal activity against P. rapae than podophyllotoxin. Also, the antifeedant activities showed that these compounds exhibited less potency than podophyllotoxin.     

Synthesis and antitumor activities of novel benzoylphenylurea derivatives.

Seventy novel benzoylphenylurea compounds were synthesized and their antitumor activities were examined in vivo against P388 leukemia. N-(2-Nitrobenzoyl)-N'-[4-(2-pyrimidinyloxy)phenyl]ureas showed the highest antitumor activities when dosed intraperitoneally or orally. Their structure-activity relationships were examined with particular focus on the position and the variety of substituent on each aryl ring.     

Synthesis,antioxidant and antitumor activities of some of new cyclobutane containing triazoles derivatives

Abstract

Thiosemicarbazides (2a–e) were obtained by the interaction of furan-2-carboxylic acid hydrazide (1) with five different isothiocyanate (RNCS) derivatives. By addition of KOH to the reaction medium, ethyl, allyl, phenyl and benzyl, p-tolyl substituted 1,2,4-triazoles (3a–e) were obtained. 3a–e were dissolved in dry acetone containing K₂CO₃ in the presence of 2-chloro-1-(3-methyl-3-mesitylcyclobutyl) ethanone (4) to give 3,4,5-trisubstituted 1,2,4-triazole sulfanyl compounds containing a cyclobutane ring (5a–e). The structures of the final compounds were confirmed by elemental analyses, FT-IR, ¹H-NMR and ¹³C-NMR. The antioxidant and antitumor properties of the synthesized compounds were also investigated. Three of the triazole derivatives with p-tolyl, benzyl and phenyl substituents (5c–e) displayed good antioxidant and antitumor activity in comparison to the standards.     

Synthesis of novel phthalazine derivatives as pharmacological activities

Phthalazine derivatives attached to amino acid derivatives were synthesized with high yields. The reaction of phthalazine derivatives with different phthalyl and tosylamino acids such as glycine, alanine, phenylalanine, valine, serine, and threonine in the presence of N,N-dicyclo hexylcarbodiimide (DCC) as a dehydrating agent reagent yielded high yields of the afforded compounds. Phthalylamino acids derivatives were obtained by deprotection of phthalazine derivatives, with the latter heating with hydrazine hydrate. The chemical structures of all phthalazine derivatives were affirmed by elemental analysis and spectral data (IR, MS, ¹HNMR, and ¹³C NMR). Screening out and estimation of the synthesized derivatives for their cytotoxic and antioxidant activity were done, and most of them showed powerful activity in comparison with standard drugs.     

Synthesis, structure, and anticholinesterase activity of some organophosphorus derivatives of anabasine

Anabasine derivatives based on methylphosphonothoic acid have been synthesized. It has been shown by PMR spectroscopy that in solution O-alkyl O-[-(anabasin-1-yl)ethyl] methylphosphonothioates exist in two stereomeric forms, which is due to the influence of the optically active anabasine residue. It has been shown that these compounds are competitive reversible inhibitors of acetylcholinesterase and of butyrylcholinesterase.Institute of Bioorganic Chemistry of the Uzbek SSR Academy of Sciences, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 561–565, July–August, 1987.     

Synthesis,structure, and anticholinesterase activity of some organophosphorus derivatives of anabasine

Anabasine derivatives based on methylphosphonothoic acid have been synthesized. It has been shown by PMR spectroscopy that in solution O-alkyl O-[β-(anabasin-1-yl)ethyl] methylphosphonothioates exist in two stereomeric forms, which is due to the influence of the optically active anabasine residue. It has been shown that these compounds are competitive reversible inhibitors of acetylcholinesterase and of butyrylcholinesterase.