Nghien CIFU - Ky tnuat
Tai li§u tham khao 1. 06 Huy Bich. Dang Quang Chung, BOI XuSn Chuang v^ CS. (2006), CSy thuoc vi nhuvg dgng vH lam thudc d Vi^t Nam. NXB Khoa hpc v& KT thu§t.
Tap 1, trang 1039-1044
2. Do Tdt Lpi (1995), Nhimg ciy thudc vi vi thudc Viet Nam. NXB Khoa hpc v^ Ky thu§t, trang 47-48
3. Boalino D. M., McLean S.. Reynolds W. F,.
Tinto W. F. (2004), "Labdane diterpenoid of Leonurus sibiricus". J. Nat. Prod.. 67(4), p. 714-717.
4. Hersel U., Steck M., Seifert K. (2000). "A new route to 2,7- and 7-functionalized labdanes". Eur. J.
Org. Chem., p. 1609-1615.
5. Monta H., Gonda A., Takeya K., Itokawa H., litaka Y. (1997), "Cycloleonunpeptide D. a new proline-nch cyclic decapeptide from Leonurus heterophyllus", Tetrahedron, 53(5), p. 1617-1626.
6. Phan M. G., Phan T. S,, Matsunami K., Otsuka H. (2005), "New labdane-type diterpenoids from Leonurus heterophyllus Sw.", Chem. Pharm. Bull, 53(8), p. 938-941.
7. Wu H., Froczek F R., Ferreira D., Burandt 0.
L., Zjawiony J. K. (2011), "Labdane diterpenoids from Leonurus sibiricus". J. Nat. Prod.. 74 (4), p. 831-836.
Tong hop va khao sat tac dung khang khuan cua chavicol va dan chat lien quan
H^ Le Dan Thao, Triroing Ngpe TuyIn, Tran Cdt Dong, Tran Thanh Dao*
Khoa Duac. Dai hoc Y Duac Thanh pho Ho Chi Minh
Oat van d l
Chavicd (4-allylptienol) la hyp chat t y nhidn dup'e dung trong edng nghlep san xuat nude hoa nhu mpt chat tao huong. Cac d i n xuat chavicol rat phd bidn trong gidi thye vdt, dac biet Id nhung cay cd thdnh phan hda hpc chinh la tinh dau. Ddn nay chua cd tdi lieu nao tim hieu ed he thong ve hoat tinh sinh hpc cua chavicol va d i n chdt. Chavicol vd dan chat lien quan Id thanh phan ehu ydu trong tinh dau la trdu klidng {Piper betle L., Pifieraceae).
l\/1ethoxychavieol edn la thanh phan chinh chidm 45- 70% trong tinh ddu huang nhu trang {Ocimum gratissmum L., LamiaeeaeJ vd huang nhu tfa {Ocimum sanctum L , Lamiaceae), cd 80-85% trong tinh dau dinh huang {Syzygium aromaticum (L.,) (Vlemet. Perry Iwlyrtaceae).'^^
IVIdt sd chavicol khac tgo thanh mpt nhdm hap ehat quan trpng trong tinh ddu cCi ridng {Alpinia galanga L., Lamiaceae) nhu I'-acetoxychavicol acetat, 1 '-acetoxy eugenol acetat, 1 '- hydrcixyehavicol acetat, 1'- hydroxychavicol Ngodi ra, trong tinh dau cua eac loai sa {Cymbopogon sp., Poaeeae) nhu eugenol.
elemiein (4-alli^-1,2,3-trimethoxybenzen)'^^.
Theo eac tac gia Nguyin Dinh Nga vd Nguydn Van Thanh, eugenol - mdt dan xuat
chavicol trong tinh ddu la trdu khdng eho hoat tinh khang Candida albicans tot'^l Ivlpt nghien cdu khac eho thay cae hydroxychavicol trong trau khong cung la mpt hap chdt co hoat tinh chong oxy hoa, chong ung thu, khang nam, khang khuan^''^...
Nghien edu nay trinh bay qui trinh tong hap va ket qua t h d nghidm hoat tfnh sinh hpc cua mpt so ddn xudt chavicol rieng re hope trong phoi hpp vdi mpt so khdng sinh trdn mpt so vi khuan nham gop thdm d u lieu ve tac dung sinh hpc cho nhdm dan ehat chavicol.
Doi tu'O'ng va phu'O'ng phap nghien CLPU
Nguyen lieu
Guaiacol, allyl bromid, benzoyl bromid va anhydrid propionic mua t d Cdng ty Acres Organic, cac hoa ehat vd dung mdi khdc ed nguon goe Tmng Quoc. Cac hda ehat va dung mdi dat tidu chudn phong thi nghiem dupe dung tryc tidp khdng tinh ehe Ipi. Cdc phan dng ddu d u p e kiem tra bdng sdc ky Idp mdng tren Silica gel 60 F254 (Merck). Diem chdy d u p e do tren may Gallenkamp. Pho IR d u p e ghi trdn may FTIR 8101 cua Shimadzu, ^H-NIVIR duae ghi
CHI DirOC HQC - 12/2012 (SO 440 NAM 52)
• Nghien ciru -• Ky thuat
trdn mdy Bruker 500 MHz vdi chudn nOi Id TMS (tetram ethyl silan).
P h u a n g phdp t6ng hp'p hda hpc Ting hiyp dSn chit eugenol vi o-eugenol
Guaiacol dup'e allyl hda vdo nhdm hydroxy ty do vd sau dd dup'e chuydn vj trong didu kidn nhidt dd cao d u d i s y hd try eua sdng vi ba tpo thdnh eugenol vd orf/ro-eugenol, theo sa dd sau:
0CH3
-^^:=^
K2CO3 •OCHa
ace Ion
r
^OCHa
guaiacol 0-allylguaiacol eugenol (e,) o-eugenol (62) S a dd 1 : Phin uvg chuyin vj Claisen tmng ting hpp eugenol vi o-eugenol /50-eugenol d u p e tdng h y p t u chinh eugenol tdc KOH ( S a dd 2). Cdc dSn chdt eugenol (alkyi thdng qua phdn ung chuydn vj tdc dgng cua xuc hode aeyl) d u p e tdng hpp theo s a dd 3.
elhy len glycol ^ O C H ,
eugenol
{2-methoxy chavicol) fso-eugenol (63) S c dd 2: Tdng hp'p iso-eugenol fi> eugenol
z
allyl bromida: anhydrid acetic/
b; anhydrid propionic/
c. benzoyl clorid eugenol
(2-methoxychavicol)
O-alkyleugenol ( e j (2-methoxychavicol) acyleugenol (eg. e^. e?) S c d 6 3: Phin ung acyl/alkyi hda eugenol (2-methoxychavicol) Khao sdt tac d^ng sinh hpc
Khio sit tic dyng khing khuan Cdc Chung vi khudn dung trong t h u nghidm:
Escherichia coli ATCC 25922; Pseudomonas aeruginosa ATCC 27853; Streptococcus faecalis ATCC 29212; Staphylococcus aureus ATCC 43300 (MRSA); Staphylococcus aureus ATCC 29213 (MSSA).
IVldi tm-dng t h d nghipm: SDA (Sabouraud Dextrose Agar); TSA (Tryptycase Soy Agar)
Xic djnh nong cfp til thiiu t>c chi vi sinh v$t (MIC) bang phuong phip pha ioin^^
Pha loang mpt day dung djch cae t h u F I C : MIC cua A trong phoi hpp
MIC cua A
nghidm trdn bdn nhya 96 gieng de ed day ehat t h u vdi ndng dd gidm ddn t d 128 - 1 pg/ml. Cho mdi trudng vd djch treo vi sinh vdt vdo cac gidng, u trong 24 g i d ddi vdi MRSA vd 16-18 gid ddi vdi vi khudn khdc, nhidt dd 37°C. Dpc ket qud bdng mdt t h u d n g . MIC Id ndng dO thap nhat uc chd s y phdt tridn cua vi sinh vdt.
Dinh Itpgng khi ning hiip dong khang khuin bing phuong phip bin cdf^^
Cdc phdi hyp cd tdc dgng uc ehd sy phdt tridn cua vi khudn thu nghidm sd dupe ehpn de tinh chi s6 d c chd ridng phdn FIC (fractional inhibitory concentration), d y a theo edng thdc sau"^:
^ MIC cOa B trong phdi hap MIC eua B Trong dd: FIC < 0.5: hi$p ddng; 0,5 < FIC < 2: cdng hgp, FIC > 2: di khing.
TAP CHi DirgiC H Q C - 12/2012 (S6 440 NAM 52)
• N g h i i n CLFU - Ky thuat
K e t q u a v a b a n l u ^ n Ket qua tong h a p
Tong bgp 4-allyl-2-methoxyphenol (e-,) vi 6-allyl-2-methoxypheno! (e^
Hoa tan khoang 0,05mol cdc dan xudt eua phenol n h u guaicol, eugenol trong aceton khan trong binh cau day trdn. Thdm t u t u allyl bromid (so moi gap 1,2 lan so moi eugenol), khudy ddu.
Tidp tuc cho kali earbonat khan (sd moi gdp 2 Idn s6 moi eugenol), v u a cho v d a khudy mpnh.
Dun hoi luu d 50°C - BO^C trong 8-10 g i d . Theo ddi phan ung bang sac ky Idp mdng. Khi phan ung xay ra hoan toan, dd ngupi phdn dng, Ipc d u d i dp sudt gidm. C6 quay djeh Ipc ddn hdt dung mdi aceton thu d u y e chat Idng dpng ddu, mdu vang, trong suot. Dun hdi luu d nhidt dO sdi eua phdm v u a thu d u p e trong 5-10 gid. Tinh ehe bang sac ky cdt bang silica gel 200 - 400 mesh, hp dung mdi n-hexan - aceton (10:1).
Tach d u p e 2 san pham ei vd 62.
4-Allyl-2-methoxyphenol (ei) San phdm la chdt Idng mau vang nhat, trong suot, khdng tan trong nude, tan trong methanol, aceton, cloroform, DMSO. Sac ky Idp mdng Rf 0,28 (ether dau hda:ethyl acetat 9:1); 0,31 (n- hexan:aeeton 10:1). ^H-NMR (500 MHz. CDCI3) 5 (ppm): 7,31 (1H, s, OH); 6,81 (1H, dd, J = 2,0 Hz, 7,25 Hz, Hs); 6,74-6,69 (2H, m, H3, He);
6,03-5,95 (1H, m, HCH=); 5,07-5,03 (1H, dq, J = 1,5 Hz, 4,0 Hz, Hc/ScHz=); 4,99-4,96 (1H, m.
HfranScH2=); 3,83 (3H, s, HQCHB); 3,38 (2H, d, J
=7,0 Hz, HcH2-)- Hieu sudt 9,7%.
6-Allyl-2-methoxyphenol (e^
San pham la chat Idng mau vang nhat, trong sudt, khdng tan trong nude, tan trong methanol, aceton, cloroform, DMSO. Sac ky Idp mdng Rf 0,38 (ether dau hdarethyl acetat 9:1); 0.40 (n- hexan:aeeton 10:1). ^H-NMR (500 MHz, CDCI3) 5 (ppm): 6,81-6,74 (3H, m, H3, H4, Hg); 6,05-7,95 (1H, m, HcH=); 5,70 (1H, s, OH); 5,10-5,04 (2H, m, HcH2=); 3.88 (3H, s, HQCHS); 3,41 (2H, d, J=6,5 Hz, HcH2-). Hipu sudt 67%.
Tong hpp 2-methoxy-4-(propenyl)phenol (e^
Cho khoang 0,01 moi eugenol vdo binh edu day trdn, thdm 15 ml ethylenglycol. Sau do them KOH khan so moi gap 7,3 lan). Khudy hoi luu ed gia nhipt khodng 130-150°C. Theo ddi phdn dng bang sdc k j Idp mdng. Khi phan ung xay ra hoan toan, de nguOi djch phdn dng. Thdm 10 ml nude
cat, acid hda djch bang acid clorid dpm ddc den pH 2- 3. Chiet djeh thu dupe vdi 3 x 10 ml diethyl ether, thu djeh ether, loai bd idp nude. Ldm khd djch ether vdi natri sulfat khan. Lopi bd ether thu djch mdu ndu den, Tinh chd bdng sac ky ept siliea gel vdi hp dung mdi ethyl acetat 9:1.
Sdn phdm (tl Id trans/eis: 83,3/16,7) Id chdt Idng mdu vdng nhpt, trong sudt, khdng tan trong nude, tan trong methanol, aceton, clorofomi, DMSO. Sdc ky Idp mdng Rf: 0,27 (ether ddu hda:ethyl acetat 9:1); 0,30 (n-hexan:aceton 10:1). ^H-NMR(500MHz, CDCl3)5(ppm):6,86- 6,83 (3H, m. Ha, Hg, Hg); 6,34-6,31 (1H, m, HcH=); 6,11-6,04 (2H, m, HCH=); 5,56 (1H, s, OH);
3,90 (3H, s, H0CH3); 1,87-1,85 (3H, d, J = 1,5 Hz, 6,5 Hz. HcH3). Hipu sudt 58%.
4-Allyl-1-allyloxy-2-methoxybenzen (e^
San pham Id chat Idng mdu vdng nhpt. trong sudt, khong tan trong nude, tan trong methanol, aceton, cloroform, DMSO. Sdc ky idp mdng Rf 0,42 (ether dau hda:ethyl acetat 9:1); 0,51 (n- hexan:aceton 10:1). ^H-NMR (500 MHz, CDCI3) 5 (ppm): 6,82 (1H, d, J= 8,0 Hz, He); 6,71 (1H, dd, J = 1 , 5 Hz, 8,0 Hz, H5); 6,69 (1H, d, J = 1,5 Hz, H3); 6,11-6,04 (1H, m, HCH=); 5,99-5,92 (1H, m, HCH=); 5,39 (1H. dd, J = 1,5 Hz, 17,5 Hz, HcHz=); 5,27 (1H, dd, J = 1,5 Hz. 10 Hz, HCH2=);
5,10-5,05 ( 2 H , m, HCHZ=); 4.59 (2H, dd, J = 1 Hz, 5,5 Hz, HocHz); 3,86 (3H, s, HOCHS); 3,33 (2H, d, J=6,5 Hz, HcH2.)- Hieu suat 62%.
Tong hgp 4-allyl-2-methoxyphenyl acetat, 4-allyl-2-methoxyphenyl propionat vi 4-allyl- 2-methoxyphenyl benzoat
Cho khoang 0,01 moi eugenol vao binh cau day tron. Sau dd them tde nhan acyl hda (anhydrie acetic/anhydric propionic/benzoyl clorid, so moi gdp 2 idn eugenol), khudy ddu.
Tidp tuc cho 1 gipt acid sulfuric dam dpe (ngoai t r u khi dung benzoyl clorid). Khuay hoi luu ed gia nhiet khodng 65-75°C. Theo ddi phdn ung bang sac ky Idp mdng. Khi phan ung xdy ra hoan todn, de ngudi phan dng, cho them 10 ml nude eat rdi chidt vdi diethyl ether trong binh lang gan. Tiep tgc rda djeh chidt ether vdi 3 x 10 ml natri bicarbonat bao hoa. Djeh chiet ether thu d u p e lam khd vdi natri sulfat khan. Bay hai ether thu djeh ed dac mdu vdng nau. Tinh chd bang sac ky cpt hope ket tinh trong dung mdi thich hpp, thu cac san pham eg, ee va e7.
TAP CHI DirgfC HOC - 12/2012 (SO 440 NAM 52)
• Nghien ctru - Ky thuat
4-Allyl-2-methoxyphenyl acetat (e^
Sdn phdm Id chdt Idng mdu vdng nhpt. trong sudt. khdng tan trong nude, tan trong methanol, aceton, cloroform, DMSO. Sde ky Idp mdng: R(
0.29 (ether ddu hdaethyl acetat 9:1); 0,32 {n- hexan:aceton 10:1). ' H - N M R (500 MHz, CDCI3) 6 (ppm): 6,94 (1H, d, J= 8.0 Hz, He); 6,79-6,75 (2H, m, H3. H5); 6,00-5,92 (1H, m, HCH=). 5.13-5.08 (2H, m. HcHzO; 3,82 (3H, s, HOCHS): 3.37 (2H, d, > 6,5 HZ, HCH!-): 2,30 (3H, s, HCHS). Hidu sudt 42%.
4-Allyl-2-methoxyphenyl propionat (e^
Sdn phdm Id chdt Idng mdu vdng nhpt, trong sudt, khdng tan trong nude, tan tnsng methanol, aceton. elorofonm, DMSO Sdc ky idp mdng Rf 0,36 (ether ddu hda:ethyl acetat 9:1); 0,42 (n- hexanaceton 10 1) ^H-NMR (500 MHz, CDCI3) 5 (ppm): 6,94 (1H, d, J= 8,0 Hz, He); 6,78-6,75 (2H.
m, H3, Hs); 6,00-5.92 (1H. m. HCH=); 5.12-5,08 (2H, m, HcH2=); 3,81 (3H, s, HQCHS): 3,37 (2H, d, J= 6,5 Hz, Hew); 2,60 (2H, q, J = 2.5 Hz, H^tKCHs); 1,27 (3H. t, J= 2.5 Hz. HcHZQhds). Hidu sudt 5 1 % .
4-Allyl-2-methoxyphenyl benzoat (or) San pham la bpt mdu trdng dye, ed dnh kim, khdng tan trong nude, tan trong methanol, aceton, elorofonn, DMSO Nhipt dp ndng chdy 69-70 °C.
Sac ky idp mdng R, 0,44 (ether ddu hda:ethyl acetat 9:1); 0.46 (n-hexan:aceton 10:1). Pho IR (em"
V 1737,7 (uC=0); 1247,0 (6OCH3). ' H - N M R (500 MHz, CDQs) 6 (ppm): 8,21 (2H, dd, J = 1,5 Hz, 8,0 Hz, Hj.. He); 7,64-7,60 (1H, m, H4); 7,50 (2H, t, J=
8,0 Hz. H3, Hff); 7,06 (1H, d, > 8 , 0 Hz, Hg); 6,84- 6,80 (2H. m. H3, H5); 6,03-5,95 (1H, m, HCH=); 5,14- 5,09 ( 2 H , m, HCH23); 3,80 (3H, s, OCH3); 3,41 (2H, d, J=6,5 Hz, HcH2-)- Hipu suat 60%.
Kit qua khio sat tic dyng khing khuan Cdc chung vi khuan trude khi t h u nghipm da d u y c ddnh gia dpt tidu chudn theo h u d n g ddn c u a C L S I , M100-S2l'^.
T h y e hipn trdn chung vi khuan chudn Staphylococcus aureus ATCC 25923 theo p h u a n g phdp khdng sinh do. Ket qud eho thdy d u d n g kinh vdng vd khuan cua eae khdng sinh trdn cdc chung vi khuan ehuan deu ndm trong gidi han eho phdp eua CLSI, M100-S21.
Tien hanh theo qui trinh d u p e md td d trdn.
Ket qua tdm tdt trong bdng 3.
Ket qua cho thay: e i , e j va 63 deu cd hopt tfnh khang khuan trdn E. coli, S. faecalis v d MSSA. Ngodi ra, 62 vd 63 ed hoat tinh khdng khudn tren P. Aeruginosa, va MRSA.
Kdt qud dinh l u v n g khd ndng hidp ddng cua d i n chdt vd khdng sinh
T d kdt qud djnh tinh trdn, chpn cdc edp cd t u o n g tdc d u a n g tinh trdn cdc chung vi khudn t h u nghidm Id ede ddi t u y n g d u y c khdo sdt djnh l u p n g tdc dgng hidp i^^ng theo md hinh thd nghidm Checkerboard. Tinh todn gid trj MIC ridng re vd MIC trong phdi hpp. gid trj FIC theo h u d n g ddn ei^a CLSI. Kdt qud tdm tdt trong cdc bdng 1 . 2 v d 3.
Bdng 1 : Kit qui djnh luring hi$p ding cua 62 vdi cic khing sinh
VI khuin
C$p phii hVP
Gii trj MIC (pg/ml) Filing
r§
Phii hpp
fy^ Kit
Gii « " f f lu^n
tri ^°f' Miu
FIC ' ' ; ; „ tmmg khing . '
sinh " ' ^ Vanco
8!
Spira Genta Tobra 82 Clinda Spira Genta 62 Tobra
62 2 1024
8 1024
0,5 1024 0,25 1024 1024 1024 1024 1024 4 1024
64 1024
1 512
2 512 0,125
512 0.0625
64 64 256 64 512 2 256
16 512
1,0 0,75 0,75 0,31 0,31 0,56 0,75 0,75
2 (llinj 4 4 4 4 16 2 4
C«ng h(rp C«ng h(rp CJng HiSp d6ng Hi«p (l6ng COng hep C«ng
hgrp COng hyp Tren MSSA. d i n chdt 82 cd tdc dgng cpng h a p v d hidp ddng vdi cae khdng sinh vancomycin, spiramycin, gentamiein, trong khi dd trdn MRSA ddn chdt 62 cd tdc dgng c$ng hp-p vd hidp ddng khi phdi h p p vdi clindamydn, spiramycin, gentamiein vd tobramycin.
Ddn chdt ee cd tdc dgng cdng hpp vdi 2 khang sinh spiramycin vd tobramycin trdn S. faecalis, c6 tdc dgng cdng hyp vdi clindamycin. Trdn S.
faecalis chi cd MSSA, dan chdt 62 cd tde dgng cpng hpp vd hidp "J^ng vdi cdc khdng sinh nhu vancomycin, spiramycin, gentamiein, trong khi do trdn MRSA ddn chdt 62 cd tdc dyng cdng hpp va hidp dong khi phdi hpp vdi clindamydn, spiramycin, gentamidn vd tobramydn.
Trong cdc phdi hpp tren cd cdp cd tac dyng hidp ddng vdi cdc gid trj MIC ridng phdn cOa
TAP CHI DlTOC HQC - 12/2012 (S6 440 NAM 52)
' Nghien ciru - Ky thuat
chat t h u va khang sinh kha thap, do Id ede cap phdi h o p CO tidm nang: tren MSSA cd Tobra- 62; tren MRSA co Clinda- ea, Genta- 6 1 .
Bang 2: Ket qua dinh limng hiep dong cua 63 vol cac khang sinh
Gia tri MIC MCec
^ Cap (t"^"") Gia *^"3 Kiiu
^""^n f^ .i,ng Ph6l 1^ Z ' - «
re hcyp khang sinh S. ea 2048 1024 " ' ^ ^ ^ ' ' ° " ' hop faecafe Tobra 16 16 Khiong COng
ej 2048 512 ' tang hop COng Clinda 0,25 0,016 „ „ , .
63 512 256 °'^ ^^ hop
- ^ ' ^ T 512 256 ^•°'> '
COng hppGenta 0,5 0,25 Cong
hap Clinda 1024 256
63 1024 256
Cfing hap Spira 1024 256
63 1024 512
Cpng hap Cong hpp 63 1024 512
Cong hp'p Bang 3: Ket qua dinh luung hiep dong cua et vdi cac khing sinh
MIC mdi chit MIPC Cap f^g^"'^' Gia 1^"3 Kiiu
^ . phii . tri ^.°t* tuxmg khuan ^ Rieng Phoi p(^ Jmh ,^^
•^ re hop khang sinh Clinda
ei Tobra
ei Clinda
ei Genta MRSA ei
Tobra ei
0,25 1024 0,25 1024 1024 1024 4 1024
64 1024
0,0625 256 0,0625
512 256 512 1 128
16 512
0,50 0,75 0,75 0,38 0,75
16 (lan) 16
4 4 4
COng hop Cong
hop Cong
hop Hiep dOng COng hop Nhan xet vi kha nang tang hoat tinh khing khuan cua cic dan chat eugenol tong hpp
Tren Streptococcus faecalis
Phdi hap giua spiramydn hoac tobramydn va ea Id ph6i hop cd tac dung tnjng binh trdn S.faecalis.
TAP CHI DirgfC HOC -12/2012 (S6 440 NAM 52)
MIC cua khdng sinh gidm 4 lan va 2 lan.
Tren Staphylococcus aureus nhay dm vdi methiclllin (MSSA)
Phoi hpp giua clindamydn vd es la phoi hpp eae tde dung mpnh, MiC eua khang sinh giam 16 Idn.
Phoi hpp giua spiramycin hoac gentamiein hope tobramydn vd 62; cdc phdi hpp giua spiramycin hope tobramydn va ei id phoi hpp ed tde dyng trung binh, lam giam MIC eua khdng sinh 4 lan.
Phdi hap giua amikacin hope gentamidn vd ea Id phdi hpp co tac dung trung binh, MIC cua khang sinh gidm 2 lan.
Tren Staphylococcus aureus di khang methiclllin (MRSA)
Phoi hpp giua dindamyein hope spiramydn vd 62 Id phoi hap cd tac dung mpnh, MIC cua khdng sinh giam 16 lan.
Phoi hap tobramydn va e2; dindamyein hoac spiramycin hope gentamiein hope tobramycin va ea; cae phoi hpp clindamycin hoac gentamiein hope tobramycin va ei id phoi hap cd tac dung trung binh, MIC cua khang sinh giam 4 Idn.
Phdi hpp gentamiein va 62 la phdi hpp ed tac dyng tmng binh, MIC cua khang sinh giam 2 Idn.
K i t luan
Trong cong trinh nay, qui trinh t6ng hap cac ddn chdt chavicol da d u a c nghien cdu. Phan ung didu chd kha dan gian va hieu sudt tong hap kha cao. Cac d i n chdt tong hop da d u p e xac djnh cau true qua cac pho phan tich. Tac dgng khang khuan cua cac d i n chdt tong hpp ndi chung khong manh. Cac ddn chdt eugenol (ei), o-eugenol (62), isoeugenol (63) cd hopt tinh khang khuan trdn 5 ehung vi khuan vdi MIC 5 512, trong khi cac d i n xudt cdn lai. (e^-e?) deu khdng co tfnh khang khuan, tuy nhien trong cac phoi hpp vdi khang sinh, cae ddn chat chavicol cdn mang nhom hydroxy t y do lam tang hopt tinh cua khang sinh cd y nghTa t u 4-16 lan.
Nhom allyl khi gdn vao nhan tham d vj tri oriho- hoac para- deu cho tac dyng khang khudn vdi MIC tuang duang nhau.
Cac hap chat chavicol vdi nhdm OH t y do cd tae dung tang tinh nhay cam eiia Streptococcus faecalis, MSSAva MRSA vdi khang sinh phdi hop.
S u m m a r y
Seven derivatives of eugenol (2- methoxychavlcol) were synthesized from
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