Sinteza i farmakološko ispitivanje novih 4-(3-etilfenil)-1-supstituiranih 4H-[1,2,4]triazolo[4,3-a]kinazolin-5-ona kao nove klase H1-antihistaminika

A series of novel 4-(3-ethylphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones (4a-j) were synthesized by the cyclization of 3-(3-ethylphenyl)-2-hydrazino-3H-quinazolin-4-one (3) with various one-carbon donors. The starting material, compound 3, was synthesized from 3-ethyl aniline by a new innovative route with improved yield. When tested for their in vivo H1-antihistaminic activity on conscious guinea pigs, all test compounds protected the animals from histamine induced bronchospasm significantly. Compound 4-(3-ethylphenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one (4b) emerged as the most active compound of the series and it is more potent (74.6 % protection) compared to the reference standard chlorpheniramine maleate (71 % protection). Compound 4b shows negligible sedation (10 %) compared to chlorpheniramine maleate (30 %). Therefore compound 4b can serve as the leading compound for further development of a new class of H1-antihistamines.Ciklizacijom 3-(3-etilfenil)-2-hidrazino-3H-kinazolin-4-ona (3) s različitim donorima jednog C atoma sintetizirana je serija novih 4-(3-etilfenil)-1-supstituiranih 4H-[1,2,4]triazolo[4,3-a]kinazolin-5-ona (4a-j). Početni spoj 3 pripravljen je iz 3-etil anilina na novi, inovativni način, s poboljšanim iskorištenjem. U testovima in vivo na zamorcima, svi testirani spojevi pokazali su značajno zaštitno djelovanje protiv bronhospazma induciranog histaminom. Spoj 4-(3-etilfenil)-1-metil-4H-[1,2,4]triazolo[4,3-a]kinazolin-5-on (4b) najaktivniji je među testiranim spojevima (zaštita 74.6 %) i jači od referentnog standarda klorfeniramin maleata (zaštita 71 %). Spoj 4b pokazuje zanemarivu sedaciju (10 %) u usporedbi s klorfeniramin maleatom (30 %). Stoga spoj 4b može biti vodeći spoj za daljnji razvoj nove klase H1-antihistaminika

Garcinia mangostana L.: A phytochemical and pharmacological review

Garcinia mangostana L. (mangosteen, Clusiaceae) has a long history of use as a medical plant, mostly in Southeast Asia. This is a review of the phytochemistry and pharmacology of mangosteen. Traditionally mangosteen is famous for its antiinflammatory properties and is used in the treatment of skin infections and wounds. Other applications include the therapy of various conditions such as dysentery, different urinary disorders, cystitis and gonorrhoea. This review highlights the development of this botanical drug into a widely used nutraceutical. Products derived from G. mangostana are now distributed increasingly all over the world. This has given rise to a concomitant increase in research on the phytochemical constituents and biological activity of mangosteen. Central to the biological activity of the species are xanthones which are reviewed in detail. A comprehensive assessment of the biological activities of individual xanthones as well as extracts of G. mangostana is included. In addition, its potential in terms of developing novel drug leads is assessed. Products containing its fruits are now sold widely as ‘liquid botanical supplements’, but evidence for the health benefits of these products is still lacking. As shown here, a serious weakness in our knowledge is the lack of clinical data and it is not yet clear to what extent the findings about pharmacological activities are of potential clinical relevance

Effect of γ-mangostin through the inhibition of 5-hydroxytryptamine(2A) receptors in 5-fluoro-α-methyltryptamine-induced head-twitch responses of mice

1. Intracerebronventricular (i.c.v.) injection of γ-mangostin (10–40 nmol/mouse), a major compound of the fruit hull of Garcinia mangostana Lin., like ketanserin (10, 20 nmol/mouse, i.c.v.) inhibited 5-fluoro-α-methyltryptamine (5-FMT) (45 mg kg(−1), i.p.)-induced head-twitch response in mice in the presence or absence of citalopram (a 5-hydroxytryptamine (5-HT)-uptake inhibitor). 2. Neither the 5-FMT- nor the 8-hydroxy-2-(di-n-propylamino)tetralin (5-HT(1A)-agonist)-induced 5-HT syndrome (head weaving and hindlimb abduction) was affected by γ-mangostin or ketanserin. 3. The locomotor activity stimulated by 5-FMT through the activation of α(1)-adrenoceptors did not alter in the presence of γ-mangostin. 4. 5-HT-induced inositol phosphates accumulation in mouse brain slices was abolished by ketanserin. γ-Mangostin caused a concentration-dependent inhibition of the inositol phosphates accumulation. 5. γ-Mangostin caused a concentration-dependent inhibition of the binding of [(3)H]-spiperone, a specific 5-HT(2A) receptor antagonist, to mouse brain membranes. 6. Kinetic analysis of the [(3)H]-spiperone binding revealed that γ-mangostin increased the K(d) value without affecting the B(max) value, indicating the mode of the competitive nature of the inhibition by γ-mangostin. 7. These results suggest that γ-mangostin inhibits 5-FMT-induced head-twitch response in mice by blocking 5-HT(2A) receptors not by blocking the release of 5-HT from the central neurone. γ-Mangostin is a promising 5-HT(2A) receptor antagonist in the central nervous system

Gamma-Mangostin, a Micronutrient of Mangosteen Fruit,<em> </em>Induces Apoptosis in Human Colon Cancer Cells

Recently colorectal cancer rates have increased rapidly in Taiwan. The treatment of colorectal cancer includes surgery, radiation therapy and chemotherapy. Mangosteen (<em>Garcinia</em> <em>mangostana</em>) is a famous Asian tropical fruit. γ-Mangostin is a xanthone derivative isolated from the fruit hull. In previous studies, we found evidence of anti-inflammatory and anti-brain tumor activities in γ-mangostin. In this study, we performed further studies to assess the apoptotic effects of γ-mangostin on colorectal adenocarcinoma cells HT29. γ-Mangostin showed concentration and time-dependent cytotoxic effects on HT29 cells. Microscopic observation under Giemsa staining showed that γ-mangostin induced cellular swelling and the appearance of apoptotic bodies, characteristic of apoptosis in HT29 cells. In addition, flow cytometry analysis showed an increase of hypodiploid cells in γ-mangostin-treated HT29 cells, while enhancement of intracellular peroxide production was detected in the same γ-mangostin-treated cells by DCHDA assay and DiOC6(3) staining. In view of the above results, γ-mangostin has demonstrated anticancer activity and induces apoptosis in HT29 colorectal adenocarcinoma cells. The evidence suggests that γ-mangostin could serve as a micronutrient for colon cancer prevention and is a potential lead compound for the development of anti-colon cancer agents