TONG HOP VA DANH GIA TAC DUNG KHANG VIEM IN VIVO CUA D A N CHAT POLYOXYCHALCON
Nguyen Tlii Tlm Giang*, Do Tuang Ha**, Thdi Khac Minh*, Vo Phung Nguyen*, Tran Thanh Dao*
T O M TAT
Dot van de: Cdc dan chat flavonoid dac biet clialcon hien nay duac quan tdm nghien cuu nhu Id tdc nhdn kJidng viem tiem nang.
Muc tieu: Sdng loc nhimg dan chat chalcon co tdc dung khdng viem in vivo co tlie phdt trien thdnh thuoc dieu tri klidng viem it tdc dung phu dw benli nhdn man tinh.
Phucmg phdp: Ap dung phan ung ngimg tu Claisen Schmidt detong hap chalcon. Tdc dgng khdng viem cua chai thie duac xdc dinh bdng phucmg phdp gdy viem tien diugt bdng dung didi carrageenin 1% cim Winter vd cong su.
Ket qud: 10 Ddn clwi chalcon dd dugc tong hgp vd khdo sdt tdc dong Ididng viem in vivo tren diugt nlidt trdng. Cdc dan diat 2'-hydroxydialcon co tdc dung Ididng viem in vivo manh han clialcon goc (kliong mang nhom tlie)
Ket luam Cdc dan diM polyoxychalcon, die biet T-hydroxydudcon co mang it nhat 1 nhom methoxy tien vong B dugc xem co tiem nang deplidt tnen diat khdng viem m&i.
Tit khoa: polyoxydialcone, hoat tinh khdng vicm ABSTRACT
SYNTHESIS AND EVALUATION OFANTI-INF LAMMATORY ACTIVITY OF SOME POLYOXYCHALCONES
Nguyen Thi Thu Giang, Do Tuong Ha, Thai Khac Minh, Vo Phung Nguyen, Tran Thanh Dao
* Y Hoc TP. Ho Chi Minh * Vol. 14 - Supplement of No 1 - 2010: 93 - 99 Background: Flavonoids especially chalcones recently Imve reported as potential anti-inflammatory inhibitors.
Objectives: To screen for new chalcone cotnpounds that show good in vivo anti-inflammatory activity.
Methods- Claisen Schmidt reaction is applied for syntliesis of heterocyclic chalcone, and tlieir anti- inflammatonj activity is measured by the model of carrageenin-induced edema in hind paw ofthe rat.
Results: 10 Polyoxychalcones were obtained with good yields and the results of in vivo anti-inflammatory activity showed that dialcones zmth hydroxyl group at position 2 of A ring are stronger tlian that of mother dialcone
Conclusions: The methoxy groups on B ring may be to have positive affect to tlie in vivo anti-inflammatory activity of tested chalcones. The polyoxydialcone which possessing a hydroxy givup at position C2 of A ring and at least one group methoxy in B may be consider as a lead compound for generation of new chalcone a potent anti-inflammatoiy agents.
Keyjoords: polyoxydialcone, anti-inflammatory activity
* Khoa Ducrc - Dai hoc Y Duac Tp.HCM ** Khoa Cong nghe Hoa - Truong Dai hoc Ton Diic Thing D,a chl hen be TS. T r ^ Thanh Dao DT: 0903716482 Email: tranthanhdaogiiDhcm.pdn ^•
DAT VAN DE
Hai nhom thuoc khang viem chinh hien nay dang duoc su dung nhieu la glucocorticoid va thuoc khang viem khong steroid (NSAID), ca hai thuoc nay dieu co nhieu tac dung phu thuong gap nhu kich ung, suy giam mien dich, loet da day... Su ra doi ciia cac NSAID uc che dac hieu tren cyclooxygenase-2 tuong nhu la mot giai phap moi hong dieu tri nhung Ian luot rofecoxib roi valdecoxib h\ nit khoi thi truong vi gay tang cac yeu to nguy ca tim mach.'^'™' Ref«e«e WOCT not
*'"^' Trong tinh hinh do viec nghien cuu fim ra nhirng hoat chat khang viem an toan cang h o nen het sue can thiet vi thuoc khang viem la mpt tiong 3 thuoc dung dau ve nhu cau dieu tri tinh theo gia thuoc ban ra thi truong cung voi thuoc tim mach va ung thu.
Flavonoid noi chung va dac biet la nhom chalcon da duoc nghien cuu va chung minh in viho CO tac dgng khang viem theo nhieu co che
k h a c n h a u f^"'"'- Reference soum not found) (Errari Reference source nai
found) Ve hoat tinh khang viem ciia flavonoid, rat nhieu cong hinh nghien aiu in viho va in vivo da duQC cong bo. Duong nhu co su lien quan giua kha nang chong oxy hoa va kha nang uc che eyclooxygenase va lipooxygenase,(E^'^ Reference source noi found) ^iQt SO tac gia nghien aru tac dgng khang viem in viho cua cac dan chat flavonoid nit ra nhan xet rang cac flavonoid chua nhieu nhom hydroxy va chalcon ciing cho tac dgng iic che sinh tong hgp cac chat h'en viem (prostaglandin E2, cytokin) tot hon cac dan chat
J(pia^ (Erred Reference sourcenot found). {Error; Reference source noi found)
Hien nay cac flavonoid dugc nghien cuu co tac dung tot da phan la cac flavonoid thien nhien nhu kaempferol quercetin, catechin, chrysin...
Theo cac nghien cuu, tac dung sinh hoc cua chung nho vao su co mat ciia nhieu nhom hgp chat OH phenol tu do.'^f Tuy nhien, cac nhom OH tu do nay cung la nguyen nhan lam tang su phan cue, hap thu kem nen tac dgng in vivo thuong khong tot nhu hong in vitro.
Trong mot s6 nghien cuu tnroc day, cac tac gia Haeil Park, Tran Thanh Dao (2004) da co
nhung cong bo ve tac dung khang viem in vitro a i a mgt so dan chat polyoxyflavonoid (chalcon va flavon).'^"'' ««*"«"« ^o-"" ""' iound).(Eiiot'
Reference source not found),(Ei™r' Reference source not found) \ ' ^
muc heu sang lgc chat co tiem nang phat trien thanh thuoc dieu hi khang viem, nghien cuu nay da hen hanh khao sat tac dgng khang viem in vivo hen chugt nhat trang hen mo hinh gay viem voi carrageenin 1%. Lien quan caii tnic va tac dung khang viem in vivo cung duoc ban luan de dinh huong cau hue can thiet cho tac dung khang viem trong nghien cuu tong hgp.
BCaTTJONG-FHirONGKiAFNGHIENCLrU Hoa hpc
Tat ca nguyen lieu tong hgp dugc mua tu cong ty Aldrich va Merck, sir dung true tie'p khong tinh che lai. Xac dinh nhiet do nong chay hen may Gallenkamp voi nhiet ke khong hieu chinh. Ghi pho UV hen may U-2010 (HITACHI) va pho IR tren may FTIR 8201 PC (SHIMADZU), pho "H-NMR do hen may Brucker (500 MHz).
Fhan iing ngung tu Claisen-Schmidt ""i dugc dung tong hgp dan chat chalcon (So do 1).
Sa do 1. Plidn img Claiseii Schmidt dimg tohg liap polyoxydialcon
Cho vao erlen dan chat polyoxyaeetophenon va dan chat polyoxybenzaldehyd vdi ty le moi 1:1. Hoa tan tu th hon hgp nguyen lieu voi mgt lugng toi thieu methanol, cho tir tir lugng KOH tuong duong 2 Ian so moi vao. Tien hanh 6 nhiet do phong, theo doi bang sac ky lop mong, dung moi khai trien n-hexan - aceton (5-2). Add hoa tir til hon hgp bJng H Q 10% den pH khoang 4.
Tua hinh thanh dugc lgc, rua bang nuoe lanh, ket tinh lai tiong hon hgp methanol thu san pham. Say san pham 6 40<I.
Khao sat tac dung khang viem in vivo TTiii thie nghiem: ehuot nhat trSng truong thanh khong ke gioi tinh, chung DDY, nang tir 18-22 g, khoe manh do vien Pasteur Nha trang cung cap. Chugt duoc nuoi eho quen voi moi truong 2 ngay truoc khi tien hanh thu nghiem.
Trong suot qua trinh thu nghiem, chuot dugc cung cap day du thuc an va nuoc uong.
Chdt doi chieu: ketoprofen nong do 2,5%, dang kem.
Chai gdy viem. carrageenin duoc cung cap boi Sigma Aldnch Dung dich carrageenin 1%
pha hong dung dich sinh ly dugc chuan bi truoc khi thu nghiem 2 gio.
Dung cu do the tich chdn diugt: thie't bi Pletiiymometer model 7140, hang Ugo basUe.
Khdo sdt tdc dgng khdng viem '^': chugt duge gay viem bang each tiem vao gan ban chan tiai 0,025 ml dung dich carrageenin 1%. Do the tich chan chugt 3 gio sau khi tiem. Cac chugt co the tich chan sung phii tren 50% so voi binh thuong duge lira chgn cho thu nghiem. Chupt dugc chia ngau nhien thanh eac 16, moi 16 8-10 con: 16 thii nghiem dimg kem nong dg 2,5% va 5% cua cac dan chat Flavone; 16 thuoc doi ehung dimg kem ketoprofen nong do 2,5%; 16 chung dimg kem ta dugc; 16 hang kh6ng diing kem. Theo doi the tich simg phu cua chan chugt moi ngay vao 1 gio nhat dinh trong 6 ngay lien tiep.
Miie dp phil chan chugt dugc tinh theo cong thuc
Vo X: muc do phil tinh theo %
Vo: the tich chan chugt truoc khi gay viem (don vido 1/100 ml)
Vn: the ti'ch ehan chugt sau khi gay viem (don vi do 1/100 ml)
Phuong phap thohg ke mo ta dugc sir dung de tinh gia hi trung binh cua the tich chan chuot Du lieu dugc trinh bay dudi dang so trung binh (Mean) ± SEM. Su khae biet giira
cac 16 dupc phan tich b ^ g phuong phap Kruskal-Wallis, sau do la Mann-\Vhihiey voi phan mem Minitab 14.0. P<0,05 dugc cho la co y nghia thong ke.
KET QUA v A BAN LUAN Tong hop
Tu cac polyoxj'acetophenon va polyoxybenzaldehyd, 10 dan chat polyoxychalcon dupe tong hpp (xem Bang 1) va phan ti'ch cau tnic b5ng cac pho phan ti'ch IR, UV va NMR.
Bdng 1. cdu true cdc ddn chdt polyoxychalcon tdng hap (Gl-GlO)
R O STT Chat
thu- R1 R2 R3 R4 1 Gl OCH3 OCH3 H H OCH3 OH 2 G2 OCHS H ( X ; H 3 H OCHS OH 3 G3 OCH3 H H OCH3 OCH3 OH 4 G4 H OCH3 0CH3 H OCHS OH 5 G5 H OCH3 0CH3 0CH3 OCHS OH 6 G6 H H Cl H OCHS OH 7 G7 ( X : H 3 OCHS OCHS H OCHS OH 8 G8 OCHS H OCH3 0CH3 OCHS OH
9 G 9 H H H H H H
10 GIO OCHS H OCHS H H OH 2'-Hydroxy-2,3,4',6'-tetramethoxyckalcon(Gl)
Hieu sudt: 70%. Nhiet do nong chay: 1 2 1 ^ . Ph6 UV (Uaxnm, dicloromethan): 229, 346. Ph6 IR (vem-', KBr): 1625,9 (uc=o), 1579,6 (uc< nhan thom), 1110,9 (uc-o)
Pho 'H-NMR (500MHz, DMSO, 6 ppm):
13,364 (s, IH, OH phenol); 7,876 - 7,884 (d, J = 16 Hz, IH, H3); 7,799 - 7,768 (d, ] = 16 Hz, IH, H>);
7,344 - 7,309 (t, J = 9 Hz, 8,5 Hz, IH, H5); 7,168 - 7,125 (dd, J = 8,5 Hz, 8,5 Hz, 2H, H4va He); 6,116- 6,612 (d, J = 2 Hz, IH, Hy); 6,136 - 6,132 (d, J = 2 Hz, IH, H5); 3,893 (s, 3H, OCH3); 3,841 (s, 3H, OCH3); 3,828 (s, 3H, OCH3); 3,782 (s, 3H, OCHs).
2'-Hydroxji-2,i,4',6'-tetramethoxychalcm<G2) Hieu suat 56%. Nhiet dp nong chaj': 132 °C.
Pho UV (Am,, nm, dicloromethan): 227, 379. Pho m (van-', KBr): 1548,7 (uc<i), 1504,4 (DC^ nhan thom), 1118,6 (vc^>)
Pho 'H-NMR (500MHz, DMSO, 6 ppm):
13,785 (s, IH, OH phenol); 7,906 - 7,875 (d, J - 15,5 Hz, IH, Hp); 7,802 - 7,770 (d, J - 1 6 Hz, IH, H„); 7,645 - 7,628 (d, J - 8,5 Hz, IH, Hs), 6,652 - 6,648 (d, J - 2 Hz, IH, Hs); 6,634- 6,612 (dd, J = 2,5 Hz, 2,5 Hz, 8,5 Hz, IH, tt); 6,144 - 6,140 (d, J = 2 Hz, IH, tt); 6,110 - 6,106 (d, J - 2 Hz, IH, ft); 3,907 (s, 3H, OCH)); 3,897 (s, 3H, OCHs);
3,838 (s, 3H, O C t t ) ; 3,819 (s, 3H, O C t t ) . 2'-Hydroxy-2,5,4:',S'-tetramethoxychalcon(G3)
Hieu suat: 60%. Nhiet dp nong chay: 141°C.
Pho UV (Am,, nm, dicloromethan): 228, 268, 333, 380. Pho IR (vcm->, KBr): 1622,0 (t)co), 1566,1 (Dc< nhan thom), 1180,4 (Deo-). Pho 'H- NMR (500MHz, DMSO, 6 ppm): 13,443 (s, IH, OH phenol); 7,850 - 7,811 (dd, J - 16 Hz, 2H, Hp va tt); 7,220 - 7,215 (d, J = 2,5 Hz, IH, tt);
7,064 - 7,046 (d, J = 9 Hz, IH, Hi), 7,031 - 7,077 (dd, J = 3 Hz, 3 Hz, 9 Hz, IH, H * 6,162 - 6,157 (d, J = 2,5 Hz, IH, tt'); 6,127 - 6,123 (d, ] - 2 Hz, IH, Hr); 3,890 (s,3H,OCH3); 3,842 (s,3H, OCH3); 3,825 (s,3H,OCtt); 3,770 (s,3H, O C t t ) . 2'-Hydroxy-5,4,4',6'-tetramethoxychalccm{G4)
Hieu suat: 72%. Nhiet dp nong chay: 130
"C. Pho UV (A™- nm, dicloromethan): 227, 374.
Pho IR (vcm>, KBr): 1780,2 (uc<.), 1548,7 (uc^
nhan thom), 1303,8 (uc*). Pho 'H-NMR (500MHz, DMSO, 6 ppm). 13,373 (s, IH, OH phenol); 7,665 - 7634 (d, J - 15,5 Hz, IH, Hp);
7,620 - 7,589 (d, J - 15,5 Hz, IH, tt); 7,299 - 7,281 (dd, J = 7 Hz, 2 Hz, 2H, tt va tt); 7,032 - 7,015 (d, I - 8,5 Hz, IH, Hs); 6,159- 6,154 (d, J - 2,5 Hz, IH, ft); 6,122-6,117 (d, J = 2,5 Hz, IH, ft); 3,890 (s, 3H, OCHj); 3,830 (s, 3H, O C t t ) ; 3,819 (s, 3H, O C t t ) ; 3,815 (s, 3H, OCft).
2'-Hydroxif-3,4,5,4',6'-pmtamethoxifchalcon (G5J
Hieu suat: 65%. Nhiet dp nong chay: 150 <:.
Pho UV (Armu nm, didoromethan): 227, 365. Pho IR (van-', KBr): 1633,6 (wo), 1562,2 (uc^ nhan thom), 1188,1 (DC*). Pho 'H-NMR (500MHz, DMSO, 6 ppm): 13,115 (s, IH, OH phenol); 7,673 - 7,642 (d, J = 15,5 Hz, IH, Hp); 7,574 - 7,543 (d, J - 15,5 Hz, IH, H4; 7,040(s, 2H, tt va tt); 6,166 - 6,162 (d, J = 2 Hz, IH, ft); 6,129 - 6,124 (d, J - 2,5 Hz, IH, Hs); 3,880 (s, 3H, OCtt); 3,841 (s, 6H, OCtt); 3,820 (s, 3H, OCHs); 3,711 (s, 3H, OCtt).
4-Cloro-2'-hydroxy-4',6'-dimethoxychalc(m(G6}
ffieu suat 69%. Nhiet dp nong chay: 138 C Pho UV (Anmnm, dicloromethan): 230, 244. Pho IR (vem', KBr): 1629,7 (ueo), 1568,0 (DC< nhan thom), 1290,3 (uc*). Pho 'H-NMR (500MHz, DMSO, 6 ppm): 13,309 (s, IH, OH phenol); 7,766 - 7,734 (t, J = 8p Hz, 7,5 Hz, 16 Hz, 3H, Hpva tt.
Hi); 7,640 - 7,608 (d, J - 16 Hz, IH, tt); 7,515 - 7,498 (d, J = 8,5 Hz, 2H, ft va H-.); 6,166 - 6,162 (d, J = 2 Hz, IH, ft); 6,136 - 6,131 (d, J - 2,5 Hz, IH, ft); 3,895 (s, 3H, OCtt); 3,827 (s, 3H, OCtt).
2'-Hydroxy-2,3,4,4',6'~pentamethoxychalcon(G7}
Hieu suat 75%. Nhiet do nong chay: 135 °C.
Pho UV (Amxnm, dicloromethan): 228, 368 Php IR (vem', KBr): 1637,5 (ueo), 1593,1 (lK< nhan thom), 1112,9 (uc*). Pho 'H-NMR (SOOMHz, DMSO, 6 ppm): 13,541 (s, IH, OH phenol); 7,816 - 7,784 (d, J = 16 Hz, IH, Hp), 7,759 - 7,728 (d, J = 15,5 Hz, IH, H„); 7,496 - 7,749 (d, J = 8,5 Hz, I f t tt); 6,923 - 6,905 (d, J = 9 Hz, IH, tt); 6,157 - 6,152 (d, r = 2,5 Hz, IH, tt); 6,124 - 6,119 (d, J - 2,5 Hz, IH, ft); 3,892 (s, 3H, OCtt); 3,862 (s, 3H, OCft); 3,850 (s, 3H, OCtt); 3,823 (s, 3H, OCfti);
3,776 (s, 3H, OCtt).
2'-Hydroxy-2,4,5,4',6'-pentmnethoxychalcon(G8) Hieu suat: 57%. Nhiet dp npng chay: 150 -C. Pho UV (A™.nm, dicloromethan): 225, 372, 400. Pho K (vem-', KBr). 1618,2 (ueo), 1558,4 (ueo nhan thom), 1128,3 (ue*). Pho 'H-NMR (SOOMHz, DMSO, 6 ppm): 13,659 (s, IH, OH);
7,918-7,887 (d, J - 15,5 Hz, IH, Hp); 7,766-7,734 (d, J=16 Hz, IH, H„); 7,208 (s, IH, ft); 6,751 (s,lH, HJ); 6,148-6,143 (d, J - 2,5 Hz, IH, ft);
6,109-6,104 (d, J - 2 , 5 Hz, IH, tt); 3,898 (s, 3H,
OCH-.y, 3,891 (s,3H,OCH3); 3,871 (s,3H, OCH3);
3,817 (s,3H, OCH3); 3,780 (s, 3H, OCH3).
Chalcon (G9)
Hi?u suat 68%. Nhiet dp nong chay 55 "C.
IR ((vem', KBr) : 1660 (ueo), 1600 (uc^ nhan thom). ^H NMR (500 MHz, CDCb, 5 ppm): 6,9 (d, J = 17 Hz, IH, H,) 7,3 - 7,9 (m, IIH, Hb va Ar-H).
2,4-Dimethoxychalcon (GIO)
Hieu suat 54%. Nhiet dp nong chay: 132 °C.
iH-NMR (500 MHz, CDCI3 6 ppm): 7,7-7,8 (m, 2H); 7,5-7,65 (m, 3H); 7,3-7,4 (m, 4H); 6,45-6,6 (m, 2H), 3,8 - 3,95 (s, 6H, OCH3).
Ket qua thu khang viem tren chupt cua cac dan chat chalcon
Tat ca cac chalcon tong hpp dupe (G1-G8) deu CO boat tinh khang viem tot, khoi phat tac dung ngay tir ngay dau tien \ a duy tri cho den khi ket thiic thir nghiem (ngoai trir G6 khoi phat tac dvmg vao ngay thu 2). Tae dung giam do phu chan chugt tai cac thoi diem thu nghifm oia cae chat G1-G8 (6 ca 2 nong do 2,5% va 5%) so voi 16 chung khae biet co y nghia thong ke (xem Do thi 1,2, 3).
I G5S% I X3h X1 X2 X3 X4 X5 X6
Thd'i gian
DD thj 1. Do phil chdn chugt (%) tai cdc thai diem cua cdc lo thir nghiem dan chat chalcon G1,G3, G5 (2,5% vd 5%) so vai 16 chimg vd 16 ketoprofon
Do thi 2. Do phu chdn chugt (%) tqi cdc that di^n cita cdc 16 thir nghiem ddn ch& chalcon G2, G4, G6 (2,5% vd 5%) so vai 16 chumg vd W ketoprofen
Cac chat thtr nghiem Gl, G5 o nong do 5%
eho thay su giam dp phii chan chugt khae biet CO y nghia thong ke nhanh hon so voi 16 nong dg 2,5 % tuong ung, nhung voi eac chat con 1^
thi ca 2 16 eo tac dung tuong duong vi dy nhu G2 (xem do thi 4 va 5). Noi chung giiia 2 nong dp thii nghiem khong co su khac biet lon ve tac dung khang viem.
100.00 J 80.00
X3hX1 X2 X3 X4 X5 X6 Tho^ gian
D^o thi 3. Do phu chdn chugt (%) tqi cdc thai diem cua cdc 16 thir nghiem 07, G8 (2,5% vd 5%) so v&i lo chimg vd 16 ketcjprofen
80 0 - E 60 0 - I 40.0 8-20 0
0.0
X 3 h X I X2 X3 X4 X 5 >ffi T h f i ' i g i a n
Do thj 4. Do phil chdn chugt (%) a 16 2,5 % so v&i 5% cua Gl tai cdc thai dian
Chat thii nghiem G2, G3, G4, G7, G8 6 ca 2 nong dp va Gl, G5 6 nong dg 5% khi so sanh voi 16 doi chiing (dung ketoprofen 2,5%) thi khac nhau khong eo y nghia thong ke. Noi each khac cac chat thu nghiem nay deu co tac dung khang viem tuong duong vdi ketoprofen. Dac biet chat G7 6 nong dp 5% co gia tri dp phu giam nhieu hon so voi ketoprofen, dugc tiinh bay 6 Do thi 6.
X3h X I X2 X3 X4 X5 X6 T h d i gian
X3fi XI X2 X3
"nio^ gian
Do thj 5. Dp phil chdn chugt (%) a lb 2.5 % so v&i 5% ciifl G2 tqi cdc thai dian.
X3h XI >G X3 X4 X5 J©
Tha^i gian
Ifo thi 6. Do phil clidn chugt (%) & 16 G7 5% vd lo ketoprofen tqi cdc thai diem
Trong khi cae chat G1-G8 giam dp phu chan chugt CO y nghia th6ng ke so voi 16 chiing ngay tir nhiing ngay dau va duy tri tae dung thi 16 G9 dli khae bift co y nghia thong ke so voi 16 chirng 6 1 hoac 2 ngay dau, kh6ng duy tri (Do thi 7).
Dieu nay gian tiep cho thay cac chat G1-G8 tac dvng m^inh hon G9 la do anh huong aia cac nhom the methoxy hen vong A va B.
— Ketoprofen G9 2.5%
- G 9 51o
X3h XI X2 )(3 X4 ) S X6 Thcfigian
Bd thi 7. Do phii chan chuot (%) a 16 G9 so vai Id chung vd 16 ketoprofen
Ban luan
Nhom 2'-hydroxy quan trgng doi voi tac dung khang viem in vivo cua cac chat thii nghiem, ket qua khang viem in vivo phii hgp voi ket qua khang viem in \iho da c6ng bo truoc day. P1161 Cac dan chat 2'-hydroxychalcon deu co tac dung giam dg phu chan ehupt manh, khac co v nghia thong ke so voi 16 chiing, hong khi G9 la chalcon khong co nhom the 2'-hydrox)' eo tae dyng giam dp phii chan chugt rat \'eu.
Cac nhom methox}' co anh huong den boat tinh khang ^dem a i a chalcon. Theo tai Ueu, cac nhom methoxy tien vong B co kha nang tao Uen ket vai phan hi Arg-120 ciia enzym COX-2 dan den lie che enzj-m nay hoat dgng \'a ket qua uc che dupc qua trinh viem'^l. Trong thir nghiem nay cac dan chat ehalcon mang cac nhom methox}' tien vong B c^u eo tac dung lam giam dang ke do phu chan chugt thir nghiem. Giai thidi hien tugng nay, ngoai co die tuong tae thuoc va ftiu the qua noi hydrogen, eac nhom methoxy con gop phan giam bot tinh phan cue cua phan tir, giiip hoat chat hap thu tot hon \"ao to diiic, mo bi \iem.
GIO (2'-hydroxj'-2,4-dimethoxychalcon) kh6ng CO cac nhom the methox}' tren vong A nhung van co tac dung lam giam do phii chan chugt eo y nghia thong ke so \oi 16 ehung.
Dieu nay co the gia thuye't rang nhom methoxy tien vong A kh6ng quan hgng, co the giam bot mgt hoac hai nhom methoxy tren vong A de phan tii kh6ng cong kenh de hap thu.
Lien quan cau tnic va tac d u n g khang viem in vivo
Lien quan cau true va tae dung khang viem tren chugt nhat cac dan ehat chalcon (Gl-GlO) ket qua co the tom tat nhu sau (xem Hinh 1):
C a c nhom methoxy tien vong A co the kh6ng anh huong den boat tinh khang viem in vivo, tiong Idii cae nhom methoxy tren vong B lam tang tic dvmg khang \aem in vitro va in ^dvo cua ehalcon.
Nhom 2'-h\'droxy co anh huong quyet dinh den tac dung khang Wem m \'itio va in \'ivo cua chalcon.
Tang tac dgng khang viem cho
- - *- Co kha nang kh6ng anh huong den tac dung khang viem cua chalcon
~^~ Co kha nang lam tang tac dung khang viem cua ehalcon
Hinh 1. Anh huang ciia cdc nhom the doi v&i tdc dung khdng znem ciia chalcon
KETLUAN
Bang phan iing ngung tu giira dan chat acetophenon va dan ehat benzaldehyd hong moi truong kiem, chung t6i da tong hpp dugc 10 dan chat chalcon, trong do 9 dan chat thugc nhom 2- hydroxychalcon, 1 dan chat chalcon khong mang bat Cli nhom the nao. Cac chat nay deu dupc Idem tia cac th6ng so ly hoa va cae pho IR, UV va NMR-Hi.
Khao sat tinh khang \'iem tien chugt nhat dang cream boi ngoai da, mo lunh gay sung phii ciia Winter dimg chat gay viem la dung dich carrageenin 1%, so sanh voi chat doi chieii ketoprofen dang cream 2,5%. Ke't qua sang lpc dupe 6 din chat G2, G3, G4, G7, G8 va GIO tac dgng khang viem so voi ketoprofen khac nhau kh6ng CO y nghia thong ke tai mgi thoi diem thir nghiem. Dieu nay cho thay su trieh vpng cua eac hpp chat chalcon vira dieu che vi ketoprofen la mgt loai thoc khang viem thong dung tien thi truong.
TAI LIEU THAM KHAO
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