Isolation, Elucidation, Biological Evaluation And Microbial Transformation Of Secondary Metabolites From The Resinous Exudates Of Three Commiphora Species

The resinous exudates of three Commiphora species,C.opobalsamum,C.myrrha, and C.mukul,have been phytochemically investigated,and their cytotoxicities against human prostate cancer cells have also been evaluated.A total of twenty-five new secondary metabolites,including nine cycloartane-type triterpenoids,one rearranged dammarane-type triterpenoid,one aliphatic alcohol glycoside,two steroids,and twelve sesquiterpenoids,were isolated from above three Commiphora species.The essential oil of C.opobalsamum and C.myrrha was extracted hydrodistillation using a Clevenger-type apparatus,separated by gas chromatography(GC),and identified by GC-MS.The antifungal activity was also tested.In addition,microbial transformation of cycloartane-type triterpenoid was carded out,and two new compounds were obtained.Twenty-seven compounds,including cycloartane-type nine tfiterpenoids(1-9),an aliphatic alcohol glycoside(10),fifteen sesquiterpenoids(11-25),one long chain aliphatic alcohol(26),and one steroid(27) were isolated from the PE extract of C. opobalsamum,of which fifteen were new compounds.The new isolates were identified to be cycloartan-24-ene-1α,2α,3β-triol(1),cycloartan-24-ene-1α,2α,3α-triol(2),3β-acetoxy cycloartan-24-ene-1α,2α-diol(3),1α-acetoxycycloartan-24-ene-2α,3β-diol(4), 3β-isovaleroyloxycycloartan-24-ene-1α,2α-diol(5),cycloartan-24-ene-1α,3β-diol(6), cycloartan-23E-ene-1α,2α,3β,25-tetrol(7),24,25-epoxy cycloartane-1α,2α,3β-triol(8 and 9),octadeeane-1,2S,3S,4R-tetrol 1-O-α-L-rhamnopyranoside(10),eudesmane-1β, 5α,11-triol(11),guaia-6α,7α-epoxy-4α,10α-diol(12),germacr-2α-methoxy-1(10), 7(11)-dien-6-oxo-8,12-olide(13),guaia-2α-methoxy-7(11),8(9)-dien-10α-hydroxy-6-oxo-8,12-olide(14),and furanocadina-1(10),6,8-triene-4-ol(15).The new cycloartane- type triterpenoids 1-9 and aliphatic alcohol glycoside 10 exhibited moderate inhibitory effect against human prostate cancer cells PC3 and DU145 with IC₅₀ values ranging from 7.1 to 34.7μM.Furthermore,1 and 10 were able to inhibit the expression of androgen receptor(AR) in LNCaP cells.Seventeen compounds were obtained from the PE extract of C.myrrha,including five triterpenoids(28,1,7-9),and twelve sesquiterpenoids(16-20,22,32-34). Myrrhasin(28),a 30(14→13)abeo-dammarane triterpenoid,myrrhanolide A(29),a 14(10→1)abeo-eudesmane sesquiterpenoid,and myrrhanolides B-C(30-31),were four new compounds.Compound 29 and the mixture of 30 and 31 exhibited weak cytoxicity against the PC3 cell line with IC₅₀ values of 38.3 to 46.0μM,respectively.Fourteen compounds,including three steroids(35-37),ten sesquiterpenoids(24, 33-34,38-44),and one triterpenoids(1),were isolated from the EtOAc extract of C. mukul.The two steroids,stigmasta-5,22E-diene-3β,11α-diol(35),stigmasta-5,22Ediene -3β,7α,11α-triol(36),and four sesquiterpenoids,mukulolides A-B(38-39) and mukulsins A-B(40-41),were new compounds.Mukulolides A-B(38-39) were novel sesquterpenoid skeleton.Twenty-five and twenty components were identified from the essential oil of C. opobalsamum and C.myrrha,and the dominant constituents were curzerene(38.91%) and furanoeudesma-1,3-diene(30.24%),respectively.The two kinds of essential oil showed inhibitory effects against plant pathogenic fungi Fusarium oxysporum with IC₅₀ of 11.7 and 9.16μg/mL,respectively.The biotransformation of cycloartane-type triterpenoid was evaluated using fourteen microorganism,and Penicillium janthinellum was adopted to biotransform cycloartan-24-ene-1α,2α,3β-triol.Incubation of P.janthinellum afforded two products, cycloartane-1α,2α,3β,24α,25-pentaol(45) and cycloartane-1α,2α,3β,24β,25-pentaol (46).