Preparation of ferulic acid derivatives and evaluation of their xanthine oxidase inhibition activity

Several ferulic acid ethyl esters (3a-h) were synthesized under the Knoevengel reaction condition and they were further reduced to afford the respective allylic alcohol derivatives (4a-g). Some of them were evaluated for the xanthine oxidase (XO) inhibitory activity. Among them, 3h exhibited a significant inhibitory activity with an IC50 value of 1.35 x 10(-5) M, while the IC50 value of allopurinol used as the positive control was 1.49 x 10(-5) M. The study suggested that the higher acidity of the phenolic OH group in the ferulic acid derivatives might result in improved XO inhibitory activity.     

Hypoglycaemic effects of tea extracts and ent-kaurenoic acid from Smallanthus sonchifolius

Hypoglycaemic activity was observed in normoglycaemic mice orally administered with the aqueous Smallanthus sonchifolius leaf tea extract, alloxan-induced diabetic mice orally administered with ent-kaurenoic acid (1), and normoglycaemic mice intraperitoneally administered with 1 from S. sonchifolius leaves. A single dose administration of 50 mg kg(-1) BW yacon leaf tea extract demonstrated immediate but relatively short hypoglycaemic activity, with significant effects observed during 1-2 h. Similarly, administration with 100 mg kg(-1) BW yacon leaf tea extract obtained by heavy stirring in hot water demonstrated a more potent activity compared to the positive control at 1.5-2.0 h. Oral administration of 1 did not affect the blood glucose level of the alloxan-induced diabetic mice, but a single intraperitonial injection of 10 mg kg(-1) BW in normoglycaemic mice had consistent percent blood glucose reduction persisting from 1 to 2 h observation periods.     

熊果酸C-3,C-28位衍生物的合成及其抗肿瘤活性研究

以天然产物熊果酸为原料,经过氧化、酰化、酯化等反应合成了11个未见报道的熊果酸衍生物,其结构经过MS、1H NMR及元素分析确定。以氟尿嘧啶和吉非替尼为阳性对照药,经MTT法对A549和SGC-7901细胞进行初步体外抗肿瘤活性研究。结果表明,目标化合物对两种细胞株的抑制率均明显高于母体化合物,且化合物4b和5a的抑制效果高于阳性对照药,值得进一步研究。     

Amino acid derivatives with anticonvulsant activity

A series of benzylamides of N-alkylated, N-acylated or free nine cyclic and one linear amino acids as potential anticonvulsants have been synthesized. The structures of the obtained compounds were designed on the basis of the previously determined structure and physicochemical properties/anticvonvulsant activity relationship of the formerly synthesized compounds of this type. The obtained compounds were evaluated in mice after intraperitoneal (i.p.) administration, by maximal electroshock seizure test (MES test), subcutaneous (s.c.) pentylenetetrazol test (s.c. PTZ test) and by the rotarod neurotoxicity test (Tox test). The results were the basis for their classification into one of three classes of the Anticonvulsant Screening Project (ASP) of the Antiepileptic Drug Development Program (ADDP) of the NIH. Three selected compounds were tested quantitatively in rats after oral administration. The MES ED50, s.c. PTZ ED50, Tox TD50 were determined and their protective index (PI) values were calculated. Anticonvulsant activity of the most promising compound (15) was examined in different seizure models. The respective ED50 and PI values of this compound were as follows: against bicuculline, 73 and 1.4; against PTZ, 47 and 2.2; against strychnine, 73 and 1.4; against pilocarpine 156, and 0.7; against kainic acid (2-carboxy-4-isopropenyl-3-pyrrolidineacetic acid), 39 and 2.6; against AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid), 10 and 10.3 and against NMDA (N-methyl-D-Aspartic acid), 114 and 0.9.     

QSAR models for analgesic activity prediction of terpenes and their derivatives

Structural Chemistry - In the present study, quantitative structure-activity relationship (QSAR) models were developed to predict analgesic activity of some mono-/bicyclic terpenoids and their...     

Halogen derivatives of imperialine and their muscarinolytic activity

The halogenation of imperialine has given 3-chloroimperialine, 3-chloroimperialine, 3, 6, 6-trichloroimperialine, and 3-bromoimperialine. 3-Chloroimperialine was identical with a known chloroimperialine. The structures of the new compounds have been established. Their muscarinolytic activities have been determined.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, Tashkent, fax (3712) 89 14 75. Original article submitted November 7, 1994. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 269–271, March–April, 1995. Original article submitted November 7, 1994.     

Bisquaternary derivatives of cyclobuxine-D and their biological activity

Six new bisquaternary derivatives of cyclobuxine-D have been obtained, and their biological activities have been studied.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, Tashkent, fax (3712) 40 64 75. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 742–744, September–October, 1997.     

Formation of pyrazine derivatives from D-glucosamine and their deoxyribonucleic acid (DNA) strand breakage activity

Two pyrazine derivatives [fructosazine (3) and deoxyfructosazine (6)] were simultaneously formed in a solution of D-glucosamine hydrochloride under various conditions. They showed deoxyribonucleic acid (DNA) strand breakage activity in plasmid pBR322 comparable to that of D-glucosamine. The DNA strand breakage by fructosazine (3) was stimulated by Cu2+.     

Preparation and antiplatelet activity of glycidic acid derivatives

Arylalkanoic acid derivatives exhibit a variety of biological effects. In the current publication some of new glycidic acid derivatives were prepared via the Darzens condensation. The synthetic approach, analytical and spectroscopic data of all newly synthesized compounds are presented. The prepared compounds were evaluated as potential inhibitors of arachidonic acid-induced platelet aggregation and their activity was compared with that of acetylsalicylic acid as the standard. (±)-Ethyl 3-{4-[(4-methoxyphenyl)sulfanyl]phenyl}-3-methyl-cis-oxirane-2-carboxylate (IC₅₀ = 0.07 mmol L⁻¹) and (±)-3-{4-[(4-methoxyphenyl)sulfanyl]phenyl}-3-methyl-cis-oxirane-2-carboxylic acid (IC₅₀ = 0.06 mmol L⁻¹) showed the highest antiplatelet activity against arachidonic acid-induced platelet aggregation comparable with the standard. Structure-activity relationships between the chemical structure, lipophilicity, and the antiplatelet activity of the evaluated compounds are discussed.     

积雪草酸衍生物的合成及抗肿瘤活性研究

以天然产物积雪草酸为起始原料,对其C-2、C-3、C-23位羟基、C-11位氢、C-28位羧基进行结构改造,合成了13个新的积雪草酸衍生物,其结构经MS及1H NMR等确证。采用MTT法,选用高表达人癌细胞(He La、Hep G2和BGC-823)对它们进行初步的体外抗肿瘤活性研究,结果表明,所测化合物对He La、Hep G2和BGC-823肿瘤细胞的抑制活性均明显强于积雪草酸,其中化合物I4和II4对He La、Hep G2和BGC-823细胞表现出很强的抑制活性,明显高于已上市药物吉非替尼,值得进一步研究。     

Structures and biological activity of cinnamoyl derivatives of coumarins and dehydroacetic acid and their boron difluoride complexes

Computer-assisted screening for Kohonen self-organizing maps in terms of the quantitative structure??activity relationship (QSAR) model revealed the high potential activity of cinnamoyl derivatives of coumarin and dehydroacetic acid and their boron difluoride complexes against a number of biological targets, including HIV-1 integrase. The pronounced inhibitory properties of dehydroacetic acid derivatives and their boron difluoride complexes against HIV-1 integrase were experimentally confirmed by in vitro testing of their antiviral activity with respect to HIV-infected cells. The data obtained suggests a correlation between the structure of the compounds studied and their biological activity.     

Biological activity of selected boronic acids and their derivatives

A series of substituted phenylboronic acids and benzoxaboroles were evaluated for their antimicrobial activity. Antibacterial and antifungal action activity of several compounds was tested against Escherichia coli 67, Staphylococcus aureus 209‐p, Mycobacterium luteum VCM B‐868, Aspergillus niger VCM F‐1119 and Candida tenuis VCM Y‐70. Substituted phenylboronic acids have low biological activity against all the investigated species. Benzoxaboroles reveal higher biological activity in comparison with the corresponding acids. The highest activity was observed for small benzoxaborole molecules, and the unsubstituted benzoxaborole has only slightly lower biological activity as compared with the 5‐fluoro‐substituted one (AN2690). The compound possessing two oxaborole fragments has very high biological activity towards Mycobacterium luteum and both investigated fungi. Copyright © 2012 John Wiley & Sons, Ltd.     

Novel synthesis of zerumbone-pendant derivatives and their biological activity

Zerumbone 1, having powerful latent reactivity and containing two conjugated double bonds and a double conjugated carbonyl group is the major component of the essential oil of wild ginger, Zingiber zerumbet Smith. The conjugation system plays an important role in the expression of biological activity. N-Bromosuccinimide (NBS) reaction of 1 gave high reactive intermediate 2 with an exo-methylene group, which was obtained from 1 quantitatively. Treatment of 2 with nucleophiles gave various zerumbone-pendant derivatives, including C–H, C–O, C–N, and C–C bond formation, maintaining the conjugation system through S_N2′-type reaction. Almost all zerumbone-pendant derivatives showed a good value of IC₅₀ against the suppressive effect of NO generation. Among them, amine derivative 5, binding with 2 mol of zerumbone, showed the strongest activity (IC₅₀: 0.24 μM).     

Novel NO-releasing derivatives of betulinic acid with antitumor activity

Thirteen novel NO-releasing derivatives of betulinic acid (BA) bearing two types of NO-donors (nitrates and furoxans) were synthesized and evaluated for their antitumor activity. The results showed that furoxan-based derivatives exhibited higher antitumor activity than nitrate-based derivatives, with compounds 11a and 11b displaying promising potency against B16 cell lines and HepG2 cell lines (IC50 < 1 μmol/L). Wesupposed that NO-releasing amount of these derivatives which can be detected by Griess method may contribute more to their antitumor activity. As a result, furoxan-based derivatives released larger amount of NO than that of nitrate-based derivatives, which partially explained the higher anti-tumor activity of the former.     

Antitrypanasomal activity of novel benzaldehyde-thiosemicarbazone derivatives from kaurenoic acid

A series of new thiosemicarbazones derived from natural diterpene kaurenoic acid were synthesized and tested against the epimastigote forms of Trypanosoma cruzi to evaluate their antitrypanosomal potential. Seven of the synthesized thiosemicarbazones were more active than kaurenoic acid with IC?? values between 2-24.0 mM. The o-nitro-benzaldehyde-thiosemicarbazone derivative was the most active compound with IC?? of 2.0 mM. The results show that the structural modifications accomplished enhanced the antitrypanosomal activity of these compounds. Besides, the thiocyanate, thiosemicarbazide and the p- methyl, p-methoxy, p-dimethylamine, m-nitro and o-chlorobenzaldehyde-thiosemicarbazone derivatives displayed lower toxicity for LLMCK? cells than kaurenoic acid, exhibing an IC?? of 59.5 mM.     

Synthesis and cytotoxic activity of usnic acid cyanoethyl derivatives

Cyanoethyl derivatives of usnic acid (natural lichen metabolite) were prepared. The reaction proceeded as a C-alkylation process via addition of two acrylonitrile molecules. Cytotoxic effect of the synthesized derivatives on the blood tumor cell lines was studied.     

Kinetics of oxidation of alkanes and their derivatives byn-decanepersulfonic acid

The kinetics of interaction ofn-decanepersulfonic acid with linear, branched, and substituted hydrocarbons was studied. The oxidation ofcyclo-C₆H₁₂/C₆D₁₂ occurs with a moderate kinetic isotope effect,k ^H/k ^D=2.2±0.3. A satisfactory correlation between the partial rate constants and the structure of hydrocarbons in terms of the Okamoto-Brown equation was found. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 5, pp. 822–825, May, 2000.