New diterpenoid glucoside and flavonoids from Plectranthus scutellarioides (L.) R. Br.

Abstract Three new compounds, diterpenoid glucoside (13S,15S)-6β,7α,12α-trihydroxy-13β,16-cyclo-8-abietene-11,14-dione 7-O-β-D-glucoside 1, flavonoids apigenin 7-O-(3′′-O-acetyl)-β-D-glucuronide 2 and apigenin 5-O-(3′′-O-acetyl)-β-D-glucuronide 3, together with known compounds caffeic acid 4, luteolin 5-O-β-D-glucoside 5 and rosmarinic acid 6 were isolated from the aerial parts of Plectranthus scutellarioides (L.) R. Br. The structures of the new compounds were elucidated by spectroscopic and mass-spectrometric analyses, including 1D- and 2D-NMR. Compound 1 inhibited hyaluronidase by 25% at the concentration of 200 μM, compounds 2 and 3 showed inhibitory activity on butyrylcholinesterase better than standard galanthamine at the concentration of 100 μM, and compound 6 is a potent antioxidant with an ORAC value of 2.15 ± 0.12

Acid-Base Initiated Cyclization and Retrocyclization Reactions of Ethyl 2-(3-Acylselenoureido)benzoates, -thiophene-3-carboxylates and the Corresponding 2-(3-Acylisoselenoureido) Derivatives

Acid and base initiated cyclization and retrocyclization reactions of the selenoureas 1-6 and isoselenoureas 7-12 to fused 4H-1,3-selenazine and 1,2,3,4-tetrahydropyrimidine-4-one skeletons are reported. Fused 2-acylamino-4H-1,3-selenazine-4-ones 13-18 were formed by the action of concentrated sulfuric acid on acylselenoureas 1-6 or on 2,2-dimethylpropanoylisoselenoureas 10-12 at room temperature. On the other hand, benzoylisoselenoureas 7-9 were not obtained in this cyclocondensation under the same conditions. The reaction of potassium ethoxide on selenazines 13-18 in the ethanol solution evoked retrocyclization to the starting acylselenoureas 1-6. Both types of the title compounds, i.e. selenoureas 1-6 and isoselenoureas 7-12, were deprotonated in a methanol solution of potassium hydroxide used in an equimolar amount, giving rise to potassium salts 19-24, which were isolated only for the thiophene series. By heating the separated potassium salts 20, 21, 23 and 24 in the methanol solution provided, deacylation and isoselenoureas 26, 27 were formed. The in situ prepared salts 19, 22 cyclized under the same conditions with deacylation to 4-selanyl-3,4-dihydroquinazoline-4-one 28. The title compounds 1-6, 7-12 and products of their deacylation 26, 27 on boiling in methanolic potassium hydroxide cyclized to the corresponding fused 2-selenoxo-1,2,3,4-tetrahydropyrimidine-4-one potassium salts. These compounds provided pyrimidine-4-ones 28-30 on acidification. Acid initiated retrocyclization 28-30 to the corresponding 2-amino-4H-1,3-selenazine-4-ones was unsuccessful. C, H, N, Se elemental analyses, FTIR, 1H-NMR, and 13C-NMR spectroscopies supported the structure of synthesized compounds.A short review on cardiotonic steroids and their analogues is presented. The natural, semisynthetic and synthetic derivatives, as well as their mechanism of action and structure-activity relationships are shown, with a special reference to aminoguanidine derivatives

Synthesis and Characterization of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4-Propoxybenzoates and Their Hydrochloride Salts

Five new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates were designed and synthesized as potential dual antihypertensive agents. The compounds were prepared as free bases and subsequently transformed to hydrochloride salts. The position of protonation of nitrogen atoms in the piperazine ring of hydrochloride salts was determined by means of 13C-CP/MAS and 15N-CP/MAS NMR and IR spectroscopy. Using these solid-state analytical techniques, it was found that both nitrogen atoms were protonated when excess hydrogen chloride was used for preparation of salts. On the other hand, when the equimolar amount of hydrogen chloride was used, piperazine nitrogen substituted by aryl was protonated

New P-S-N containing ring systems. Reaction of 2,4-(naphthalene-1,8-diyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide with N, N-bis(trimethylsilyl)methylamine.

From the reaction of 2,4-(naphthalene-1,8-diyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide 1 with methylbis(trimethylsilyl)amine 2 in dichloromethane a product of the P2S2 ring cleavage, (C10H6)P(S)(SSiMe3)(mu-S)P(S)(NMeSiMe3) 3, was isolated, existing in an equilibrium between two diastereomeric forms in solution. Compound 3 was also obtained when toluene was used as a solvent. Its subsequent reaction with pyridine (py) led to the desilylated ionic product [Hpy(+)][(C10H6)P(S)(NHMe)(mu-S)PS2-] 4, which reacts with tetraphenylphosphonium chloride to give [PPh4+][(C10H6)P(S)(NHMe)(mu-S)PS2-] 5. When acetonitrile was used as a solvent a cage compound 2,6-(naphthalene-1,8-diyl)-3,4-dimethyl-1,3,5,2 lambda(5),6 lambda(5)-thiadiazadiphosphinine 2,6-disulfide 6 containing a six-membered CN2P2S heterocycle was obtained. The new compounds were studied spectroscopically (1- and 2-D high resolution NMR, IR, MS) and in the cases of 3, 5 and 6 by X-ray crystallography.</p

Synthesis, Analysis, Cholinesterase-Inhibiting Activity and Molecular Modelling Studies of 3-(Dialkylamino)-2-hydroxypropyl 4-[(Alkoxy-carbonyl)amino]benzoates and Their Quaternary Ammonium Salts

Tertiary amines 3-(dialkylamino)-2-hydroxypropyl 4-[(alkoxycarbonyl)amino]benzoates and their quaternary ammonium salts were synthesized. The final step of synthesis of quaternary ammonium salts was carried out by microwave-assisted synthesis. Software-calculated data provided the background needed to compare fifteen new resulting compounds by their physicochemical properties. The acid dissociation constant (pKa) and lipophilicity index (log P) of tertiary amines were determined; while quaternary ammonium salts were characterized by software-calculated lipophilicity index and surface tension. Biological evaluation aimed at testing acetylcholinesterase and butyrylcholinesterase-inhibiting activity of synthesized compounds. A possible mechanism of action of these compounds was determined by molecular modelling study using combined techniques of docking; molecular dynamics simulations and quantum mechanics calculations

Identification of Key Structural Characteristics of <i>Schisandra chinensis</i> Lignans Involved in P‑Glycoprotein Inhibition

The aim of the present study was to determine the structural requirements for dibenzocyclooctadiene lignans essential for P-glycoprotein inhibition. Altogether 15 structurally related lignans isolated from <i>Schisandra chinensis</i> or prepared by modification of their backbone were investigated, including three pairs of enantiomers. P-Glycoprotein inhibition was quantified using a doxorubicin accumulation assay in human promyelotic leukemia HL60/MDR cells overexpressing P-glycoprotein. A preliminary quantitative structure–activity relationship analysis revealed three main structural features involved in P-glycoprotein inhibition: a 1,2,3-trimethoxy moiety, a 6-acyloxy group, and the absence of a 7-hydroxy group. The most effective inhibitors, (−)-gomisin N (<b>1</b>) and (+)-deoxyschizandrin [(+)-<b>2</b>], were selected for further evaluation of their effects. Both these lignans restored the cytotoxic effect of doxorubicin in HL60/MDR cells and when combined with a subtoxic concentration of this compound increased the proportion of G2/M cells significantly, which is a usual response to treatment with this anticancer drug