• N g m e r T c l F u - K y t h u a t dau danh gia hoat tinh androgen cua re bach benh (Eurycoma longifolia J.) trgn chupt thyc nghiem, Tap chi Duoc hoc, (2009), so 404 nam 49: 16-20
2. Dewsbury Effects of tetrabenazine on the copulatory behavior of male rats. European Journal of Pharmacology, (1972), 17: 221-226
3. Anders Agmo, Male rat sexual behavior, (1997), Brain Research protocol 1: 203-209.
4. Ang HH et al , Eurycoma longifolia Jack enhances libido in sexually experienced male rats, Exp. anim, (1997), 46(4): 287- 290.
5. D.Giuliani, A.Ottani, F.Ferrari, Influence of sildenafil on copulatory behaviour in sluggish or normal ejaculator male rats: a central dopamine mediated effect?. Neuropharmacology, (2001), 42: 562-567
6. Elaine M.Hull and Juan M., Dominguez Sexual behavior in male rodents, Horm. Behav (2007), 52
(1): 45-55
7. H.H Ang and K.L Lee, Effects of Eurycoma longifolia Jack on orientation activities in middle- aged male rats, Blackwell Science Fundamental &
Clinical Pharmacology (2002), 16: 479-83
8. Hooi Hoon Ang and Meng Kwoon Sim Eurycoma longifolia Jack and orientation activities in sexually experienced male rats, Biol. Pharm., (1998), Bu//21 (2): 153-5
9. James R. Wilson, Norman Adler, Burney Le Boeuf, The effects of intromission frequency on successful pregnancy in the female rat. Psychology, (1965) Vol. 53:1392- 1395
10. P. Zanoli, M. Zavatti, C.Montanari, M. Baraldi, Influence of Eurycoma longifolia on the copulatory activity of sexually sluggish and impotent male rats, Journal of Ethnophanvacology, (2009), 126: 308-13
T 6 n g h o p ^ - ( b e n z o I i / j t h i a z o l - l - y O - N 4 - hydroxysuccinamid va dan chat hudng
uc che histon deacetylase
Dao Thi Kim Oanh,' Sang-Bae Han,2 Nguyin Hai Nam1
SB6 mon Hoa dirge, Trudng Dgi HQC Dugc Hd Noi
2Khoa Dugc, Dgi hqc Chungbuk, Han Quoc Dat vdn de
Histon deacetylase (HDAC) la nhdm cac enzym xiic tac cho qua trinh deacetyl h6a nh6m E-N acetyl lysin amino acid d phan dudi cua histon. Ngudi ta 6a chirng minh dugc trong nhieu te bao ung thu cd su huy ddng qua muc cac enzym HDAC, gay ndn cac sai Idch trong qua trinh phidn md, din den hinh thanh cac khoi
ul u l. Cac chat ire chd enzym HDAC dang trd
thanh cac tac nhdn chong ung thu day then vpng. Trong dd chat ire che HDAC la din chit cua acid hydroxamic dang dugc nhieu nhd khoa hpc quan tdm'3 , 4'. Nhdm muc dich nghien ciru ting hgp cdc din chit acid hydroxamic hudng ire chi HDAC vd sdng Ipc de tim ra chit cd hudng tdc dung khdng te bdo ung thu, chiing tdi
<Ja vd dang tiin hdnh thidt k i vd tdng hgp mdt sd din chit acid hydroxamic. Bdi bdo ndy cdng bi kdt qua tdng hgp vd thu tdc dgng ire chd enzym HDAC cua ddy cdc din chit
N1-(benzo[d]thiazol-2-yl)-N4-hydroxysuccinamid.
T h y c n g h i e m va kdt qua - Dung mdi, hda chdt vd dung cu
Cdc hda chit, dung mdi thdng thudng dugc nhdp tir cdng ty Merck hodc Sigma-Aldrich vd dugc su dung tryc tiip khdng tinh chi thdm.
Nhidt dd ndng chay dugc do bing mdy do didm chay nhidt didn. Sdc ky Idp mdng sir dyng ban mdng nhdm trdng sdn silicagel GF-254. Phd hdng ngoai dugc ghi bing mdy GX-Perkin- Elmer. Phd cpng hudng tir hat nhdn 1H dugc ghi bing mdy Bruker AV-500 diing DMSO-d6 lam dung mdi. Dd chuyen djch hda hpc (8) dugc bieu thj bdng dan vj phin tridu (ppm), liy mdc Id pic cua chit chuin ndi tetramethylsilan (TMS).
Phd khdi lugng dugc ghi bdng mdy khdi phd HP-5989-MS, LC-MSD-Trap-SL.
Tdng hgp cdc d i n chdt
Cdc din chit duac tdng hap theo sa dd sau:
TAP CHI DUQC HQC - 4/2011 (S6 420 NAM 51) 47
Acid 3-(benzo[d]thiazol-2-yl carbamoyl) propanoic va d i n chit
Acid 3-(benzo[d]thiazol-2-yl carbamoyl) propanoic (2a). Can 450 mg (3 mmol) 2- aminobenzothiazol vao binh ciu day trdn dung tich 50 ml. Hda tan bing 5 ml DMF roi them 300 mg (3 mmol) anhydrid ^succinic; 0,45 ml pyridin.
Khuiy hdn hep phan img trong 24 gid. Sau dd, chuyen tir tir hdn hgp sau phan Ceng vao 50 ml nude lanh, xuit hien tua. Loc va ri>a tua bing nirdc cit. Siy tua d nhiet dd 70°C, thu dirge san phim kit tinh hinh kim, mau tring. Hiiu suit:
82,0%; mp: 241-243°C; R, = 0,2 (DCM:MeOH, 9:1). IR (KBr, cm1): 3300-2400 (OH acid), 1697 (CO), 1606, 1561, 1449 (C=C), 2970 (CH2).
Acid 3-(6-methylbenzo[d]thiazol-2-yl carba moyl)propanoic (2b). Tien hanh tuong tir nhu chit (2a), nhung vdi chit ban diu la 2-amino-6- methylbenzothiazol. Hiiu suit: 45,4%; mp: 262- 263°C; Rf = 0,55 (DCM:MeOH, 9:1). IR (KBr, cm-1): 3300-2400 (OH acid), 3189 (NH), 1695 (C=0), 1612, 1560, 1470 (C=C), 2975 (CH2).
Acid 3-(6-methoxybenzo[d]thiazol-2-yl car bamoyl)propanoic (2c). Tien hanh tuong tu nhu chit (2a), nhung vdi chit ban dau la 2- amino-6-methoxybenzothiazol. Hiiu suit:
73,3%; mp: 271-272°C; R, = 0,57 (DCM:MeOH, 9:1). IR (KBr, cm1): 3400-2300 (OH acid), 3183 (NH), 1690 (C=0), 1611, 1590, 1476 (C=C), 2988, 2933 (CH2).
Acid 3-(6-ethoxybenzo[d]thiazol-2-yl carba moyl)propanoic (2d). Tien hanh tuong tu nhu chit (2a), nhung vdi chit ban diu la 2-amino-6- ethoxybenzothiazol. Hi$u suit: 80,4%; mp: 231- 232°C; R,= 0,3 (DCM:MeOH, 9:1). IR (KBr, cm'
1): 3300-2400 (OH acid), 3198 (NH), 1684 (C=0), 1611, 1559, 1462 (C=C), 2979 (CH2).
Acid 3-(6-methylsulfonylbenzo[d]thiazol- 2-yl carbamoyl)propanoic (2e). Tien hanh 48
O
3a-f A e, R = -S02CH3
f, R = -N02
tuong tu nhu chit (2a), nhung vdi chit ban diu la 2-amino-6-methylsulfonylbenzothiazol. Hiiu suit: 87,2%; mp: 270-271 °C; Rf = 0,21 (DCM:MeOH, 9:1). IR (KBr, cm'1): 3300-2400 (OH acid), 3179 (NH), 1693 (C=0), 1607, 1561, 1450 (C=C), 2974 (CH2).
Acid 3-(6-nitrobenzo[d]thiazol-2-yl carba moyl) propanoic (2f). Tiin hanh tuong tu nhu chit (2a), nhung vdi chit ban dau la 2-amino-6- nitrobenzothiazol. Hiiu suit: 84,7%; mp: 294- 295°C; Rf = 0,40 (DCM:MeOH, 20:1). IR (KBr, cm1): 3400-2400 (OH acid), 3460 (NH), 1692 (C=0), 1531, 1450 (C=C), 2951 (CH2).
N1-(Benzo[d]thiazol-2-yl)-N4-hydroxysucci namid va d i n chit
N1-(Benzo[d]thiazol-2-yl)-N4-hydroxysucci namid (3a). Can 1 mmol acid 3- (benzo[d]thiazol-2-yl carbamoyl)propanoic vao binh ciu day trdn dung tich 50 ml. Hda tan bing 3 ml DMF roi thdm 2 mmol CDI, 3 mmol triethylamin. Lie cho tan. Thdm 3 mmol NH2OH.HCI. Khuiy hon hgp phan irng trong 24 gid. Sau khi kit thuc phan ung, thdm acid HCI 2% vao hdn hgp phan ung se cd kit tua. Lpc, rua tua bing nude cit. Say khd d 70°C thu dugc san phim kit tinh mau tring. Hiiu suit:
51,2%; mp: 250-251°C; Rf= 0,58 (DCM:MeOH, 9:1). IR (KBr, cm'1): 3480 (OH acid), 3184 (NH), 1691 (C=0), 1610, 1574, 1447 (C=C), 2971, 2932 (CH2). ESI-MS: m/z 264 [M-H]+. 1H-NMR (500 MHz, DMSO-d6, ppm): 5 2,57-2,60 (2H, m, CH2); 2,72-2,7'4 (2H, m, CH2); 7,29 (1H, dt, J = 7,5 Hz, 1 Hz, H-5); 7,43 (1H, dt, J = 7,5 Hz, 1,1 Hz, H-6); 7,73 (1H, d, J = 8 Hz, H-7); 7,95 (1H, d, J = 7,5Hz, H-4).
N1-(6-Methylbenzo[d]thiazol-2-yl)-N*-hydro xysuccinamid (3b). Tien hanh tuong tu nhu chit (3a), chit ban diu phan irng Id acid 3-(6- methylbenzo[cf]thiazol-2-yl carbamoyl)propanoic.
TAP CHI Dl/OC HOC - 4/2011 (SO 420 NAM 51)
• N g h i e n C L F U - K y t h u a t Hi$u suit: 40,5%; mp: 252-253°C; R, = 0,52 (DCM:MeOH, 9:1). IR (KBr, cm1): 3437 (OH acid), 3185 (NH), 1695 (C=0), 1613, 1551, 1470 (C=C), 2976, 2927 (CH2). ESI-MS: m/z 280 [M+Hf, 247 [M-NHOHf. 1H-NMR (500MHz, DMSO-d6, ppm): 8 2,40 (3H, s, CH3); 2,57-2,60 (2H, m, CH2); 2,70-2,74 (2H, m, CH2); 7,23 (1H, d, J = 8Hz, H-5); 7,61 (1H, d, J = 8 Hz, H-4);
7,74 (1H, s, H-7).
Ni-(6-Methoxybenzo[dJthiazol-2-yl)-N4-hydro xysuccinamid (3c). Tien hanh tuang ta nhu chat (3a), chat ban dau phan ung la acid 3-(6- methoxybenzo[oT,thiazol-2-yl carbamoyl) propanoic.
Hi§u suit: 40,6%; mp: 215-216°C; R, = 0,46 (DCM:MeOH, 9:1). IR (KBr, cm'1): 3278 (OH acid), 3146 (NH), 1690 (C=0), 1614, 1557, 1477 (C=C), 2993, 2925 (CH2). ESI-MS: m/z 296 [M+Hf, 263 [M-NHOHf. 1H-NMR (500MHz, DMSO-d6, ppm): 5 2,31-2,34 (2H, m, CH2);
2,67-2,72 (2H, m, CH2); 3,80 (3H, s, CH3); 7,01 (1H, dd, J = 9 Hz, 2,5Hz, H-5); 7,55 (1H, d, J = 8 Hz; H-7); 7,61 (1H, d, J = 9 Hz, H-4).
N1-(6-Ethoxybenzo[d]thiazol-2-yl)-N4-hydro xysuccinamid (3d). Tien hanh tuang ta nhu chat (3a), chat ban diu phan ung la acid 3-(6- ethoxybenzo[d]thiazol-2-yl carbamoyl)propanoic.
Hi$u s'uit: 32,3%; mp: 231-232°C; R, = 0,54 (DCM:MeOH, 9:1). IR (KBr, cm1): 3528 (OH acid), 3235 (NH), 1701 (C=0), 1609, 1556, 1464 (C=C), 2980, 2932 (CH2). ESI-MS: m/z 308 [M-Hf. 1H- NNIR (500MHz, DMSO-d6, ppm): 8 1,34 (3H, t, J = 7 Hz, CH3); 2,56-2,59 (2H, m, CH2); 2,69-2,73 (2H, m, CH2); 4.04A08 (2H, m, -OCH2-); 7,0 (1H, dd, J
= 9 Hz, 2,3 Hz, H-5); 7,52 (1H, d, J = 2,5 Hz, H-7);
7,60 (1H, d, J = 9Hz, H-4).
N1-(6-Methylsulfonylbenzo[d]thiazol-2-yl)- N*-hydroxysuccinamid (3e). Tien hanh tuang tu nhu chit (3a), chit ban diu phan ung la acid 3-(6-methylsulfonylbenzo[d]thiazol-2-yl carbamoyl) propanoic. Hi$u suit: 51,1%; mp: 330-331°C; Rf
= 0,34 (DCM:MeOH, 9:1). IR (KBr, cm'1): 3488 (OH acid), 3210 (NH), 1703 (C=0), 1602, 1539, 1447 (C=C), 2984, 2927 (CH2). ESI-MS: m/z 342 [M-H]+. 1H-NMR (500MHz, DMSO-d6, ppm):
8 2,59-2,62 (2H, m, CH2); 2,76-2,78 (2H, m, CH2); 3,24 (3H, s, CH3); 7,93 (2H, H-4, H-5); ' 8,62 (1H, d, J= 1 Hz, H-7).
N1-(6-Nitrobenzo[d]thiazol-2-yl)-N4-hydroxy succinamid (3f). Tiin hanh tuang tu nhu chit (3a), chit ban diu phan ung la acid 3-(6-
nitrobenzotcdthiazol-2-yl carbamoyl)propanoic.
Hi$u suit: 63,6%; mp: 265-266°C; R, = 0,35 (DCM:MeOH, 9:1). IR (KBr, cm'1): 3442 (OH acid), 1692 (C=0), 1617, 1585, 1451 (C=C), 2962 (CH2). ESI-MS: m/z 311 [M+H]+ 1H-NMR (500MHz, DMSjD-d6, ppm): 8 2,60-2,62 (2H, m, CH2); 2,73-2,79 (2H, m, CH2); 7,88 (1H, d, J = 9 Hz, H-4); 8,27 (1H, dd, J = 9,3 Hz, 2,3 Hz, H-5);
9,03 (1H, d, J = 2,5Hz, H-7).
Thu> tac dung u>c c h i enzym histon deacetylase
Thu tac dung uc che enzym HDAC duoc thuc hidn tai Khoa Dugc Trudng Oai hpc Chungbuk, Chonju, Han Qudc va Vidn nghidn cuu sinh hpc vd cdng nghd sinh hpc Hdn Qudc (KRIBB). Nguydn tdc thu tdc dung uc chd HDAC Id phuang phdp djnh luang huynh quang'5'. Ndng dd thu tdc dung Id 10 ug/ml, chit ddi chidu Id TSA.
Ban luan
Su dyng phuang phdp /V-acyl hda cdc 2- aminobenzothiazol vdi tdc nhdn anhydrid succinic dd tao cdc din chat cua acid 3- [benzo(d)thiazol-2-yl carbamoyl]propanoic. Ddy Id phan ung co ban, thyc hidn dd ddng vd cho hidu suit tuang ddi cao. Pyridin dupe su dyng ddng vai trd xuc tdc cho phan ung.
Tu cdc din chit cua acid 3-[benzo(d)thiazol- 2-yl carbamoyl]propanoic (2a-f), chung tdi dd tiin hdnh phan ung amid hda vdi NH2OH.HCI dd thu dupe ddy cdc din chat acid hydroxamic (3a-f) su dyng tdc nhdn hoat hda nhdm carboxylic. Ban diu, chung tdi lua chpn N,N- dicyclohexylcarbodiimid (DCC) Id tdc nhdn hoat hda hay dupe su dyng, lai Id hda chit sdn cd tai phdng thi nghidm vd khd re tien. Tuy nhidn, kit qua tdng hap thu cho thiy phan ung xay ra khdng hodn todn. Didu ndy cd thd giai thich Id do cdc nguydn nhdn i) DCC It tan trong DMF; ii) Kha ndng hoat hda nhdm -COOH cdn ydu.
Ngodi ra, mdt nhupc diem khdc cua DCC Id san phim phu tao thdnh sau phan ung Id 1,3- dicyclohexylurea khd tan trong nude ndn rit khd loai ra khdi san phim.
Tiep tyc, lya chpn cdch hoat hda bdng cdch tao anhydrid hdn tap, chung tdi dung xuc tdc iso- butylcloroformat. Kdt qua thyc nghidm cho thiy phan ung cOng khdng xay ra hodn todn. Theo ly thuyet vd cdc tdi lidu tham khao thi vide hogt hda nhdm carboxylic tao anhydrid hdn tap tao ra tdc
TAP CHI DUOC HOC - 4/2011JSO 420 NAM 51) 49
nhan acyl h6a hoat dpng tuang doi manh. Tuy nhien, ket qua thyc nghidm cua chung tdi sau khi duyc tien hanh nhieu lan deu cho thay khdng thu duyc san pham acid hydroxamic.
Lua chpn xuc tac la carbonyldiimidazol (CDI) de tao ester hoat hda, kdt qua phan ung xay ra hoan toan, khdng cdn vet cua nguyen lidu ban dau sau phan ung. Ngoai uu diem phan ung xay ra hoan toan, khi su dung CDI lam chit hoat hda nhdm carboxylic san pham thu duyc kha tinh khiet, khdng ddi hdi qua trinh tinh che phuc tap do imidazol tao thanh va CDI du deu tan trong nude ndn dd dang loai ra khdi san phim.
Ciu true cua san phim phan ung duyc khing djnh bing cac du lidu pho MS, IR va 1H-NMR.
Pho MS cua cac chit tong hyp duyc cho pic cd so khoi diing bing khoi luyng phan tu. Do dd cd thi khing djnh san phim sau phan ung Id din chit cua N1-[benzo(d)thiazol-2-yl]-N4-hydroxy succinamid. Pho IR cua cac chit cd pic cua nhdm chuc -OH acid, nhdm -C=0 amid va NH amid. Odi vdi cdc chit tong hyp duyc, pho IR khdng cd y nghTa nhieu trong vide khdng djnh la acid hydroxamic hay din chit cua acid propanoic (nguydn lieu ban diu). Tuy nhidn, pho
Bang 1: Kit qui thu hoat tlnh (re chi HDAC
khoi cd the giiip khing djnh chdc chdn phan ung dd xay ra. Trdn pho 1H-NMR cua 6 chit deu cho du so proton cua vdng thorn vd mach nhdnh. Proton cua nhdm NH, OH do tin hidu yeu vd khdng on djnh ndn cd nhung chat khdng cho pic trdn pho do.
Sau khi tong hyp vd khing djnh cau true cua 6 chit tong hyp duoc, chiing tdi dd tien hdnh thu tdc dung uc che HDAC tai Khoa Duyc, Oai hpc Chungbuk vd Vidn nghien ciru sinh hpc vd cdng nghd sinh hpc Hdn Quoc (KRIBB). Kit qua thu hoat tlnh trinh bdy d bang 1 cho thiy chit 3c vd 3d cd uc che HDAC song cdn yiu. 6*
nong dd 10 ug/ml, chit 3c vd 3d uc che khoang 20% hoat tlnh cua enzym thu nghidm. Cd t h i ciu noi giua phin khung benzothiazol vd nhdm acid hydroxamic cdn qud ngdn ndn chua tao duyc di luc manh vdi HDAC. Tuy nhidn, ddy cung Id co sd cho cdc nghidn cuu tiep theo djnh hudng kdo dai ciu ndi ndy tuong ty nhu trudng hyp cua SAHA (N1-hydroxy-N8-phenyloctane diamid), mdt chit uc chd HDAC dd duyc nghidn cuu cd ciu ndi giira phin nhdn thorn phenyl vd nhdm hydroxamic Id 6 C.
Mau
FA
(Fluorescent absorbance) Trung binh
/moan\ Sai so chuan
STD t-test % hoat tinh cua enzym
1 2 3
Sai so chuan
STD % hoat tinh
cua enzym Nen 23,139 22,705 22,703 22,849 251
Tring 118,182 100,356 105,575 108,038 9,165 100
TSA 20,552 20,062 20,203 20,272 252 0,0001 0
3a 103,818 103,107 103,372 103,432 359 0,4335 3b 99,345 102,175 100,942 100,821 1,419 0,2490
3c 89,928 93,839 89,791 91,186 2,299 0,0366 80,26 3d 92,555 85,859 92,513 90,309 3,854 0,0366 79,23 3e 94,875 94,835 98,220 95,977 1,943 0,0896 85,88 3f 113,230 109,378 103,868 108,825 4,705 0,9010
Ghi chu: i) Phep thu- duoc tien hanh 3 lan (1, 2, 3) cho moi miu a nong do 10 fjg/ml. Ket qua liy gii trj trung binh; ii) FA: Fluorescent absorbance, phan anh muc dd~ hoat tinh cua enzyme cdn lai. Miu trang hoat tinh enzyme = 100%; iii)
TSA = thchostatin, chit uc chi HDAC dung lam chat doi chieu duong tinh & nong dd 1 fjg/ml.
Ket luan
Nhu vdy, chiing tdi dd tdng hyp duoc 6 ddn chit N1-(benzo[c(]thiazol-2-yl)-N4-hydroxysuccinamid.
Kdt qua thu hoat tinh uc che HDAC cho thiy 2 chit 3c vd 3d cd tdc dung song cdn ydu. Mdc dii vdy, k i t qua ndy van cho thiy ddy chat benzothiazol Id cd trien vpng cho nghidn ciru tiep theo nhdm tao ra mdt ddy
d i n chit acid hydroxamic mdi uc c h i HDAC.
Lai cam en: Od tdi duyc hodn thdnh nhd mdt phin kinh phi tu Chuang trinh nghidn ciru ca ban, B0 Khoa hpc vd Cdng nghd (NAFOSTED) cip cho TS. Nguydn Hai Nam vd dd tdi cip trudng cua trudng OH Duyc Hd NOi cip cho ThS. Ddo Thj Kim Oanh.
50 TAP CHf DUOC HOC - 4/2011 (S6 420 NAM 51)
• N g h i e n C L F U - K y t h u a t S u m m a r y
A series of N1-(benzo[d]thiazol-2-yi)-f\i4- hydroxysuccinamide and their derivatives were synthesized by a two-step pathway: i) reaction of succinic anhydride with 6-substituted-2- aminobenzothiazoles; ii) amidation of the resulting carboxylic intermediates with hydroxylamine. Structures of the synthesized compounds were confirmed by MS, IR, 1H-NMR.
Bioassays revealed that only two compounds 3c, 3d inhibited slight HDAC activity (approximated 20%).
Tai lieu t h a m khao
1. Jed L.H., Hua Z., Astrid M.K., Judith C.F., William K.D., Bethany L.H., Richard E.M., Alexander A.S., J. Paul S., Thomas A.M., Amino acid derivatives as histone deacetylase inhibitors, Bioorganic and Medicinal Chemistry Letters, 2008, 18, 34-38.
2. Po CC, Vishal P., William G., Patience G.,
Adegboyega K.O., Synthesis and structure-acitvity relationships of histone deacetylase inhibitors with triazole-linked cap group, Bioorganic and medicinal Chemistry Letters, 2008, 16, 4839-4853.
3. Charles M.M., Thevaki M., Jon D., Stephane S., James M.M., John P. A., Simon P.J., David M.V., Charles R.C, Structure-activity relationships of aryloxyalkanoic acid hydroxamides as potent inhibitors of histone deacetylase, Bioorganic and Medicinal Chemistry Letters, 2007, 17,136-141.
4. Dallavalle S, Cincinelli R, Nannei R, Mertini L, Morini G, Penco S, Pisano C, Vesci L, Barbarino M,- Zuco V, De Cesare M, Zunino F., Design, synthesis, and evaluation of biphenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors, Eur. J. Med. Chem., 2009,1-13.
5. Ralph M., Vishal P., Dyann F.W., Jon C, Development of a fluorescence polarization based assay for histone deacetylase ligand discovery, Bioorganic and Medicinal Chemistry Letters, 2008, 18, 2809-2812.
r r B a o c h e v i e n n e n p h o i h o p
a r t e s u n a t - p i p e r a q u i n
Dat vdn de
Artemisinin va cac din xuit la nhdm thuoc co hoat tlnh ching sot ret manh nhit hidn nay.
Nhu-ng den nay ky sinh trung (KST) khang artemisinin dd xuit hidn [ 7l Neu khdng cd bidn phdp kjp thdi va hidu qua, KST khdng thudc se phdt trien vd lan rdng. Bidn phdp de "bao vd"
artemisinin Id han che su dung cdc phdc do den thuoc vd triin khai rdng rdi cdc phdc do phoi hop.
Ndm 2006, To chuc Y te The gidi khuyen cdo si> dyng 4 che phim phoi hgp dirge, bao gom: artemether-lumefantrin, artesunat+mefloquin, artesunat+amodiaquin vd artesunat+sulfadoxin- pyrimethamin | 9'.
Trong so cdc dan xuit cua artemisinin, artesunat cd iru diem ve dd on dinh, sinh kha dyng vd dirge cho Id phu hgp nhit de sir dung trong cdc cdng thirc thudc phdi hgp'51. Trong sd 4 chd phim dirge Td chirc Y td Thd gidi khuydn
Nguyen VSn Han1, Nguyen Thj Huyen2 'Truong dai hoc Duoc Hd Npi, 2Tgp chi Dupe hoc dung, thi cd 3 chd phim Id phdi hgp cua
artesunat.
Piperaquin Id thudc chdng sdt rdt nhdm aminoquinolin dirge dung nap rit tdt vd cd ddc tlnh dugc ddng hpc thich hgp (thdi gian bdn thai ddi) dd phdi hgp vdi artesunat. 0 Vidt Nam, piperaquin ngdy cdng cd vai trd quan trpng trong didu trj sdt rdt tai cdng ddng | 2 , 6 ]. Ndu cdn nhic ddn ca hai ydu td hidu qua vd gid ca, cd le piperaquin Id mdt lira chpn hgp ly dd phdi hgp vdi artesunat.
Trdn ca sd dd, chiing tdi tidn hdnh bdo chd vd ddnh gid hoat tlnh chdng sdt rdt cua thudc phdi hap artesunat-piperaquin, vdi muc dich dua ra duac mdt phdi hap mdi cd lieu cd djnh, hiru hidu vd an todn, phii hgp vdi cdc tidu chi md Td chirc Y td Thd gidi dd khuydn cdo. Bdi bdo ndy gidi thidu kdt qua nghidn ciru vd bdo chd. Kdt qud ddnh gid ddc tinh vd hoat tlnh chdng sdt rdt se dugc trinh bdy trong sd bdo sau.
TAP C H I D U O C H Q C - 4/2011 (so 420 N A M 51) 51
