The Chemical Constituents Of Three Artocarpus Plants And Their Bioactivities

The Artocarpus genus plants(Moraceae)are mainly distributed in tropical Asiaareas such as South Asia and Southeast Asia and Pacific islands.Among them 15 species including 2 subspeciesmainly distributed in Yunnan Province,P.R.China.Most plants of this genus are evergreen trees with edible fruits.Recently,secondary metabolites isolated from Artocarpusgenus aretriterpenoids,isoprenylphenols and sterols.Literature checking revealed that Artocarpusshowed diverse activities,such asantitumor,reducing blood fat,antimalarial,antiinflammatory,antiviraland other pharmacological activities,as well as cyclooxygenase,tyrosinase,pancreatic lipase,and cathepsinK and other inhibitory activitiesIt was reported that scholars have systematically studied the chemical consituents of 25 species of Artocarpus,from which a large amount of isopentenyl phenolic compounds have been isolated,which is the main active ingredient of this genus.These compounds have a variety of biological activities and provide a good prerequisite for structural screening and structural transformation.However,the relationship between these biological activities and the clinical and folk use of these plants needs to be further confirmed,and the structure-activity relationship of these biologically active prenyl phenolic compounds needs further confirmation.In general,research on the chemical consituents and pharmacological activity of the genus is still very weak.Therefore,the medicinal value of many plants of the genus really merits further study.The three fresh marine organisms were extracted with 95%EtOH.The extracts was extracted with petroleum ether and ethyl acetate respectively.The or ganic fraction was purified by repeated silicagel,sephadex LH-20 column chromatography,and high performance liquid chromatography(HPLC)to yield 78 compounds,including 26 new compounds.Their structures including relative stereochemistry were elucidated on the basis of extensive spectroscopic analysis(NMR,MS,IR,UV,and optical rotation)and comparison with those reported data in the literature.42 compounds were isolated from A.Nigrifolius,including 14 triterpenoids,four drop terpenes(1*,11,12 and 18),6 sterols,1 benzald ehyde derivatives(6),one small molecular amine compound(2),a nutmeg acid monoglyceride(31)and 15 prenylflavonoids(27-30 and 32-42).Among of the m,1*,28*and 41*are news.Compound 2 and 31 are the first time that had been reported as a naturally occurring compound,Compounds 6,8,11,15-17,20,22 and 23 are isolated fromthe genus Artocarpus for the first time.Also,this is the first time for the report of all other compounds from the Moraceae family.14 compounds were isolated from A.chaplasha,including two known stibenes(43-44),9 new stilbenes with two isoprenoid groups(45*-53*)and three new prenylflavonoids(54*-56*).22 compounds were isolated from A.pithecogallus,including three new 18 carbon olefine acid compounds(57*-59*),6 triterp enoids(60-65),13 prenylflavonoids(66-78),and the compound 70*-73*,75*-78*are news.Compounds 27-30 and 32-42 were evaluated for their in vitro antiproliferative effects against human cervical cancer cells SiHa and human gastric cancer cells SGC-7901.The results showed thateleocharin A(39)was the most potent compound,which exhibited inhibitory activity against SGC-7901(IC50=8.3±0.2 μM)and significant cytotoxic effect on SiHa(IC50=0.7±0.1 μM),respectively.Compound 34 showed inhibitory activity against SiHa cells(IC50 8.7±0.2 μM).Compounds 40 and 42 exhibited weak activity against SiHa cell s(10 μM<IC50<20μM).Compound 32 showed inhibitory activity against SGC-7901(IC50 9.6±0.9 μM)and weak activity against SiHa(IC50 13.3±0.4μM),and compound 36 showed weak activity against SGC-7901 cells(IC50 11.9±0.1μM).The other compounds showed inactivity against both two cell lines.Based on above results,compound 39 could be considered as potential lead compound for further development of novel anti-tumor agents.In addition,the othernon-flavonoid compounds were also evaluated for their in vitro antiproliferative effects against human cervical cancer cells SiHa and human gastric cancer cells SGC-7901.The results showed that all compounds had no inhibitory activity on HeLa cells(not listed).Among of them,compounds 10,12,13 and 25 showed increased inhibitory activity,while the compound 19-21 showed weak growth inhibition activity.Amazingly,the activity of compounds 2,16,17 and 23 have reached level Moore,especially 17 and 23 com poundsshowed strong antitumor activity.The tyrosinase activity inhibition test was carried out on the flavonoids isolated from the A.pithecogallus.The results showed that some flavonoids in A.pithecogallus had different degrees of inhibition of tyrosinase activity compared with the kojic acid as the positive control.The ability of Compound 69 was the strongest,and the activity has reached level Moore(IC50 0.53 nM),which was significantly stronger than the positive control kojic acid.Combined with the compound structure,we can find:Chalcone(69)compounds have stronger inhibitory effect than flavonoids,benzo 5-membered ring flavonoids compounds,indicating that different structures of flavonoids have different effects on tyrosinase,maybe due to the enzyme activity catalyzes the difference in the molecular structure of the substrate.In addition,the inhibitory activity of 69、70、71 and 74 are also higher than that of the reference product kojic acid.Moreover,these compounds are natural components isolated from plants and have low toxic and side effects,and can be used as potential natural tyrosines.Enzyme inhibitors are further studied and utilized.