Synthesis and pharmacological activity of diterpenylnaphthoquinone derivatives

New diterpenylquinones, combining a diterpene diacid and a naphthoquinone, were prepared from junicedric acid and lapachol. The new derivatives were assessed as gastroprotective agents by the HCl-EtOH-induced gastric lesions model in mice as well as for basal cytotoxicity on the following human cell lines: Normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), and hepatocellular carcinoma (Hep G2). Several of the new compounds were significantly active as antiulcer agents and showed selective cytotoxicity against AGS cells.     

Synthesis and pharmacological activity of silyl isoxazolines 2

Silyl isoxazolines have been synthesized by [2+3] cycloaddition reaction of nitrile oxides to vinyl- and allylsilanes. The addition of 3-pyridylnitrile oxide to 1,3-divinyl-1,1,3,3-tetraphenyldisiloxane affords 1,3-bis{5-[3-(3-pyridyl)isoxazolin-2-yl]}-1,1,3,3-tetraphenyldisiloxane; the latter exists as a mixture of trans- and cis-isomers.The bond angle of the Si–O–Si fragment in thetrans-isomer equals 180(3)° and in the cis-isomer it is 162(3)°.The pharmacological properties of 4-[3-(5-trimethylsilylisoxazolin-2-yl)]pyridinium-chloride have been studied.     

Synthesis and pharmacological activity evaluation of curcumin derivatives

Curcumin 3,4-dihydropyrimidinones/thiones/imines have been synthesized using one-pot cyclocondensation of curcumin with substituted aromatic aldehydes and urea/thiourea/guanidine in the presence of chitosamine hydrochloride as a biodegradable and nontoxic catalyst under solvent-free microwave irradiation. The synthesized product was purified by crystallization from ethanol and the process does not involve any hazardous solvent. All the synthesized curcumin derivatives 4a-o were screened for antioxidant and anti-inflammatory activity. Biological activity data of the synthesized showed that most of the synthesized compounds exhibited greater antioxidant and anti-inflammatory activity than curcumin.     

Synthesis and pharmacological evaluation of potential metabolites of the potassium-competitive acid blocker BYK 405879

Four potential metabolites of the potassium-competitive acid blocker BYK 405879 (1) were synthesized which might be formed in vivo by enzymatic oxidation of the pyran moiety or the methyl groups attached to the (hetero) aromatic system. In all cases, the oxidation of the parent compound 1 was accompanied by a significant loss of pharmacological activity and by a decrease in lipophilicity. The target compounds 6, 14, 20, and 21 constitute valuable tool substances for the investigation of the metabolic fate of BYK 405879 (1).     

Synthesis of some furochromonesulfonamide derivatives with potential pharmacological activity

A number of visnagin-9-sulfonamides 1-3 have been prepared. In two instances side-products have been isolated in which the γ-pyrone ring is opened. All compounds were characterized by high-field ¹H and ¹³C nmr and mass spectra.     

Synthesis and pharmacological activity of O-(5-isoxazolyl)-L-serine

A novel isoxazole derivative, O-(5-isoxazolyl)-L-serine (OIS, 1), was synthesized by a Mitsunobu reaction of isoxazolin-5-one (4) with N-Boc-L-serine tert-butyl ester (5) and subsequent deprotection of the coupling product. Its structure was elucidated by spectroscopic analyses. The pharmacological activity of 1 was also examined with cloned glutamate receptors and transporters using a Xenopus oocyte-expressing system showing substrate activity on an excitatory amino acid carrier 1 (EAAC 1) as a glutamate transporter.     

Derivatives of hydroxybenzoic acids and their salts: Synthesis and pharmacological activity

Russian Journal of General Chemistry - Preparation of salicylic and acetylsalicylic acid esters via esterification and alkylation of the salts with alkyl halides has been examined. The effect of...     

Synthesis and anticancer activity of geldanamycin derivatives derived from biosynthetically generated metabolites

A new series of geldanamycin derivatives were synthesized using a semi-synthetic approach involving genetically engineered biosynthetic intermediates. These analogues were then evaluated for anti-proliferation activity in human cancer cell lines, SK-Br3 and SK-Ov3. Most of the synthesized compounds exhibited potent in vitro anti-proliferation activity toward both cell lines. Such compounds potently inhibited the expression of the Hsp90 client protein ErbB2.     

Isolation and structural determination of new sphingolipids and pharmacological activity of africanene and other metabolites from Sinularia leptoclados.

Two new sphingolipids, (2S,3S,4R)-1,3,4-trihydroxy-2-[((R)-2'-hydroxytetradecanoyl) amino] tricosane (4) and (2S,3S,4R)-1,3,4-triacetoxy-2-[((R)-2'-acetoxyoctadecanoyl) amino]octadecane (5) along with africanene (1, reasonably good yield), 23-demethylgargosterol (2) and batylalcohol (3) have been isolated from the soft coral Sinularia leptoclados. Preliminary studies for pharmacological activity (blind screening and toxicity studies) of africanene were conducted. Africanene exhibited in vitro and in vivo cytotoxicity, dose dependent hypotensive activity as well as antiinflammatory activity. The pharmacological and toxicity studies on africanene are being reported for the first time and findings strongly encourage further investigation. Compounds 1, 4 and 5 were studied for the antibacterial, antifungal and antiviral activity while compounds 4 and 5 were also studied for the short term in vitro cytotoxic activity.     

Synthesis of peptides related to immunoglobulin E (IgE) and the examination of their pharmacological activity

Five kinds of oligopeptides H-Asp-Ser-Asp-OH (1), H-Asp-Gly-Lys-OH (2), H-Ser-Asp-Gly-Lys-OH (3), H-Asp-Ser-Asp-Gly-Lys-OH (4), and H-Ala-Asp-Ser-Asp-Gly-Lys-OH (5) related to immunoglobulin E (IgE) were synthesized by the conventional solution method with the objective of obtaining a new type of antiallergic agent. Their pharmacological activity was examined by measuring the inhibition of the production of IgE and relaxation of the smooth muscle contraction of rabbit aorta. H-Ala-Asp-Ser-Asp-Gly-Lys-OH (5) displayed potent inhibition against the production of IgE antibody (69.6%) and relaxation against the contraction of rabbit aorta.     

Synthesis and pharmacological activity of sulfate conjugates at 6-position of N-substituted normorphine derivatives.

Three pairs of N-substituted normorphine derivatives and the sulfate conjugates at the 6-position were tested for the analgesic and antagonistic activities and the development of physical dependence in mice. The compounds examined were nalorphine, nalorphine-6-sulfate (N-6-S), N-cyclopropylmethylnormorphine (CPN), N-cyclopropylmethylnormorphine-6-sulfate (C-6-S), N-dimethylallylnormorphine (DMN) and N-dimethylallylnormorphine-6-sulfate (D-6-S). The latter two pairs were newly synthesized. The analgesic activity of C-6-S and D-6-S was equipotent to that of CPN and DMN by the acetic acid writhing test on the s.c. injection, and the activity of N-6-S was about 2 times more potent than that of nalorphine. The antagonistic activity of N-6-S, C-6-S and D-6-S to morphine analgesia was higher than that of the parent compounds by the tail pinch test on i.c.v. injection. A withdrawal sign was seen in mice treated chronically with CPN, C-6-S and N-6-S by challenge with naloxone, whereas the mice treated with DMN, D-6-S and nalorphine showed no such sign. The effect of sulfation at the 6-position on the development of physical dependence was not well associated with the effect on agonistic and antagonistic activities.     

New polymers for biomedical applications: Synthesis and characterization of acrylic systems with pharmacological activity

The synthesis and characterization of new biocompatible “Polymeric Drugs” on the basis of poly (methacrylic esters) and poly (methacrylamides) with side substituents of pharmacological interest, with analgesic, antiinflammatory, antipyretic and antiaggregating activities, is reported. The preparation of these systems was carried out following the universal model suggested by Ringsdorf, and the polymers prepared by the free radical polymerization of the corresponding acrylic monomers were characterized by ¹H- and ¹³C-NMR spectroscopies. Biocompatible hydrogels were prepared by free radical copolymerization of these monomers with HEMA. The characteristic copolymerization parameters and the microstructural distribution of comonomeric sequences were determined by NMR spectroscopy. The swelling behaviour of copolymer films was followed gravimetrically. Applications of polymer and copolymer systems are being tested in the fields of pharmacology and vascular surgery.     

Synthesis and pharmacological evaluation of pyrroloazepine derivatives as potent antihypertensive agents with antiplatelet aggregation activity

A series of 1-aminoalkyl-pyrrolo[2,3-c]azepin-8-one derivatives was synthesized and evaluated as alpha 1 adrenergic and serotonin 2 (5-HT2) receptor antagonists, with the aim of finding a novel antihypertensive agent potently exhibiting both activities. Some compounds with a 4-[4-(4-fluorobenzoyl)piperidino]butyl group at the 1-position exhibited both activities, and varied significantly in terms of the substituents at the 4-position of the pyrroloazepine ring. Among the compounds obtained in this study, (E)-1-[4-[4-(4-fluorobenzoyl)piperidino]-butyl]-4-hydroxyimino-7- methyl-1,4,5,6,7,8-hexahydropyrrolo[2,3-c]azepin-8-one (15a, SUN9221) displayed potent alpha 1-adrenergic antagonistic activity (pA2 = 8.89 +/- 0.21) and 5-HT2 antagonistic activity (pA2 = 8.74 +/- 0.22) in isolated guinea pig arteries. This compound exhibited antihypertensive activity and a duration of action equivalent to orally administered prazosin or doxazosin, 3 mg/kg, in conscious spontaneously hypertensive rats, as well as potent antiplatelet aggregation activity.     

Derivatives of the alkaloid convolvine and their pharmacological activity

A series of new convolvine derivatives based on the alkaloid from Convolvulus subhirsutus and C. pseudocanthabrica were synthesized using alkylhalides and aliphatic and aromatic acid chlorides. Results of biological tests showed that convolvine and its derivatives exhibited pronounced antihypoxic, immunomodulating, and anti-inflammatory activity.     

Synthesis of the major metabolites of Tolvaptan

Tolvaptan is a nonpeptide arginine vasopressin（AVP） V₂-receptor antagonist and used in the treatment of heart failure,cirrhosis, syndrome of inappropriate antidiuretic hormone secretion or other high-volume capacity of hyponatremia.The metabolites of tolvaptan are mainly produced by CYP3A4,including two major compounds named DM-4103 and DM-4107.Herein,the chemical synthesis of those two metabolites is described in this article for further study.     

Antimalarial activity of plant metabolites

This review covers the structures of compounds with antiplasmodial activity isolated from plants and is organized according to plant family. A total of 170 structures has been reviewed from 186 references found in the literature up to December 2000.