hgp dugc trdn chuOt nhlt theo dudng udng Id (2,189 ± 0,063g miu thir/kg chudt).
Summary
The antl-HIV/AIDS drug nevirapine was synthesized by Improvement of the method by Gharpure Milind Moreshwa et al. The reaction conditions were Investigated and modified to get nevirapine In high yield. The structures of synthesized compounds were confirmed by IR, 'H-NMR, '^C-NMR and MS. The quality of synthesized nevirapine was controlled, proved to meet the requlerments of EP 2007 and USP 32.
Key words: nevirapine, synthesis, antl-
HIV/AIDS drug.
Tai lieu tham khao
1. Bo Y T§, Quyet djnh sd 20/2006/QO-BYT ve viec phe duyet Chucng trinh hanh dong qudc gia ve phong chong lay t r u y i n HIV t u me sang con giai doan 2006-2010, Ha Noi. (2006)
2. Chinh phu, Quyet dinh s6 61/2007QO-TTG ve Chuccng trinh nghien ciru khoa hoc cdng ngh$ trgng diem quoc gia phat trien cong ngh? Hoa Duoc d i n nam 2020, Ha Noi, (2007)
3. Cue Y Te d u phdng va phong chong HIV/AIDS Bo Y Te, Bao cao ve Tinh hinh nhiim HIV/AIDS nam 2009 tai Viet Nam, Ha Npi (2009)
4. Cue Y Te d u phong va phdng chong HIV/AIDS - Bp Y Te, Bao cao ve Dich te hpc HIV/AIDS a Viet
Nam va c h i l n luge quoc gia phdng chong HIV/AIDS den 2010 va tam nhin 2020, Ha Npi (2010).
5. Le Quang Toan, Ky thuat hoa D u c c (tr.130- 144), nha xuit ban Y hgc, (1971)
6. Asean, Asean Guideline on Stability Study of Drug Product. (2005)
7. Boswell Robert Fredrick, Lo Young Sek, Method for making nevirapine , United States Patent 6,680,383. United States. (2002).
8. Bosw/ell Robert Fredrick, Gupton Bemard Franklin, Lo Young Sek , Improve method of making nevirapine, WO 2004/002988 A l , WIPO patents. (2004)
9. Gharpure Milind Moreshwa et al. An Improved Process For Industrial Manufacture of Nevirapine WO 2007/010352 A l , WIPO patents, (2007)
10. European Medicines Agency (2005), Scientific discussion, Viramune®
11. European Pharmacopoeia 6, European Directorate for the Quality of Medicine, monograph, (2007), 2255.
12. Hargrave et al, , 5,11-dihydro-6H-dipyrido(3,2- B:2',3'-E)(1,4)dia2e-pines and their use in the prevention or treatment of HIV infection, United States Patent (1994), 5, 366, 972.
13. ICH, Q1E Evaluation of Stability Data, (2004) 14. OECD guidelines for testing of chemicals Acute oral toxicity - Fixed dose procedure OECD 420.
(2001)
15. The United States Pharmacopelal Convention (2008), The United States Phannacopoeia 32
Tong h9p A^^-(benzo[rf|thiazol-2-yl)-A^-
hydroxyadipamid v^ dan chat hir6'ng m che histon deacetylase
Dao Thj Kim Oanh,' Sang-Bae Han,^ Hoang Van Hai', Tran Van Nam',Van Thj My Hue^, Nguyen Hai Nam'
Bo mon Hoa dirac, Trudng dgi hoc Dirac Hd Ngi Bo mon Hoa huu ca. Trirdng dgi hoc Duac Hd Noi Khoa Dirac, DH Chungbuk, Hdn QudcDat van d§
Histon deacetylase (HDAC) va histon acetyltransferase (HAT) ddng vai trd quan trpng trpng dieu hda qud trinh bidu thi gen. Histpn
deacetylase Id nhdm cac enzym xue tae qud trinh loai bd nhdm acetyl tu s-N-aeetyl lysin amino acid eua phin histon. Ngudi ta dd ehung minh dugc trong nhieu td bdo ung thu ed su
TAP CHi DUQC HQC - 7/2011 (SO 423 NAM 51) 55
huy ddng qua mue ede enzym HDAC, gdy nen edc sai lech trong qud trinh phidn md, d i n den hinh thanh cae khdi u '''®' Cae c h i t uc chd enzym HDAC dang trd thanh edc tae nhdn chdng ung thu ddy trien vpng nhu trichpstatin A, apicidin, trapoxin B, FK-228 '^"'°' Acid suberoylanilid (SAHA) da dugc sir dung trong didu tri u lympho td bao T dudi da. N h i m muc dieh nghien cuu tdng hgp edc ddn c h i t acid hydroxamic hudng ue chd HDAC va sdng Ipe de tim ra chat cd hudng tac dung khang td bao ung thu, ehung tdi da va dang tidn hanh thidt kd va tdng hgp mdt sd ddn c h i t acid hydroxamic.
Bai bao nay cdng bd kdt qua tdng hgp va thir tac dung ue chd enzym HDAC ciia day dan c h i t A/'-(benzo[cf|thiazol-2-yl)-A/®-hydroxyadipamid,
ThiFC n g h i e m v a k § t q u a
Dung moi, hoa c h i t va dung cu
Cae hda chat, dung mdi thdng thudng dugc nhdp tu' cdng ty Merck hoac Sigma-Aldrich va d u g c sir dung true tidp khdng tinh chd them.
Nhiet dp ndng chay d u g c do bdng may do diem chay nhiet dien. Sdc ky Idp mdng sir dung ban mdng nhdm trdng s i n silieagel GF-254. Phd hdng ngoai d u g c ghi b i n g may GX-Perkin- Elmer. Phd cdng h u d n g tu' hat nhan ' H dugc ghi b i n g may Bruker AV-500 dung DMSO lam dung mdi. Op chuyen dich hda hpc (5) dugc bidu thi b i n g dan vi p h i n trieu (ppm), l l y mdc Id pic eiia c h i t chuan ndi tetramethylsilan (TMS).
Phd khdi lugng d u g c ghi b i n g may khdi phd HP-5989-MS, LC-MSD-Trap-SL.
Tdng hap cac d i n c h i t
Cae dan c h i t d u g c tdng hgp theo sa dd sau:
OCH,
NaOH. MeOH
Methyl 5-(benzo[d]thiazol-2-yl carbamoyl) pentanoat va dan chat
Methyl 5-(benzo[d]thiazol-2-yl carbamoyl) pentanoat (2a). Can 960 mg (6 mmol) CDI vdo binh cdu day trdn dung tich 50 ml. Hda tan bdng 2 ml DCM rdi them 0,85 ml (6 mmol) acid monomethyl adipie. Khuly hoat hda trong 10 phut, Hda tan 450mg (3mmol) 2- aminobenzothiazol trong 2ml DMF rdi them vao binh c l u tren, Gia nhiet phan ung (40 50°C) ket hgp khuly t u hdn hgp phan irng trong 24 gid. Cat quay thu hdi dung mdi. Sau dd, chuyen tu tu hon hgp sau phan irng vdo 50 ml nude lanh, x u l t hien tiia. Lpc va rira tua b i n g nude cdt. S l y tiia d nhiet dp 70°C, thu d u g c san pham kdt tinh hinh kim, mdu t r i n g . Hieu suit:
80%; mp: 148-149°C; R, = 0,40 (DCM:MeOH, 30 1) IR (KBr cm''); 3273 (NH), 1716, 1693 (C=0), 1601, 1545, 1467 (C=C), 2946, 2877 (CH2). ESI-MS: 315 [M+Naf; 293 [ M + H f ; 262 [M+H-OCH3]"
3a-f
a, R = 6-H b, R = 6-CH3 c, R = 6-OCH3 d, R = 6-OC.,H5 e, R = 6-SO.CH3 f, R = 6-NO2
Methyl 5-(6-methylbenzo[d]thiazol-2-yl carbamoyOpentanoat (2b). Tidn hanh tuang tu nhu c h i t (2a), nhung vdi c h i t ban d i u la 2-amino- 6-methylbenzothiazpl. C h i t kdt tinh mdu tring.
Hieu suit: 84%; mp: 171-172°C; Rf = 0,43 (DCM:MeOH, 30:1). IR (KBr, cm''); 3277 (NH), 1720, 1693 (C=0), 1606, 1546, 1461 (C=C), 2946, 2874 (CH2). ESI-MS: 329 [M+Naf; 307 [M+Hf'
Methyl 5-(6-methoxybenzo[d]thiazol-2-yl carbamoyl)pentanoat (2c). Tien hdnh tuang ty nhu c h i t (2a), nhung vdi c h i t ban dau la 2- amino-6-methoxybenzothiazol. Chat kdt tinh mau t r i n g . Hieu suit: 7 1 % ; mp: 157-158°C; Rf - 0,41 (DCM:MeOH, 30:1). IR (KBr. cm''); 3270 (NH), 1716, 1690 (C=0), 1607. 1549, 1460 (C=C), 2951, 2875 (CH2). ESI-MS: 345 [M+Naf;
323 [M+Hf-
Methyl 5-(6-ethoxybenzo[d]thiazol-2-yl carbamoyOpentanoat (2d). Tien hdnh tuang ty nhu c h i t (2a), nhung vdi c h i t ban d i u Id 2- amino-6-ethoxybenzothiazol. C h i t kdt tinh mdu
56
TAP CHi DUQC HQC-7/2011 (SO 423 NAM 51)
tring. Hidu suit: 76%; mp: 164-165°C; R, = 0,42 (DCM:MeOH, 30:1). IR (KBr cm''); 3235 (NH), 1720, 1696 (C=0), 1606, 1571, 1554 (C=C), 2950, 2871 (CHj). ESI-MS: 337 [M+H]*'
Methyl 5-(6-methylsulfonylbenzo[d]thiazol -2-yl carbamoyOpentanoat (2e). Tien hdnh tuang tu nhu c h i t (2a), nhung vdi c h i t ban d i u la 2-amino-6-methylsulfonylbenzothiazol. Chit ket tinh mdu tring. H'teu suit: 6 1 % ; mp: 195- 196°C, R, = 0,40 (DCM:MeOH, 30:1), IR (KBr cm''). 3307 (NH), 1729, 1698 (C=0), 1599, 1531, 1469 (C=C), 2956 (CH2). ESI-MS: 369 [M-Hf'
Methyl 5-(6-nitrobenzo[d]thiazol-2-yl carbamoyl)pentanoat (2f). Tidn hdnh tuang t u
nhu chat (2a), nhung vdi chat ban dau la 2- amino-6-nitrobenzothiazol. C h i t kdt tinh mau vang nhat. Hieu suit: 59%; mp: 203-204°C; R, = 0,38 (DCM;Me0H, 30:1), IR (KBr cm''); 3245, 3219 (NH), 1714, 1698 (C=0), 1574, 1540, 1465 (C=C), 2960 (CH2). ESI-MS: 336 [M-H]*'
A/'-(Benzo[d]thiazoI-2-yl)-/V^- hydroxyadipamid va d i n chit
N'-(Benzo[d]thiazol-2-yl)-N^-
hydroxyadipamid (3a). Can 292mg (Immol) c h i t 2a vao binh c l u day trdn dung tich 50 ml, Hda tan bing 3 ml MeOH roi them 280mg (4 mmol) NHsOHHCl, Lam lanh binh c l u b i n g hdn hgp nudc da - mudi an. Them 320 mg NaOH (Bmmol) hda tan trong 1 ml nudc vao binh c l u tren. Khuly hdn hgp phan ung trong 1 gid 30 phut d 0°C. Sau khi kdt thue phan ung, chuyen t u tir hdn hap phan ung vao 30 ml nudc lanh, acid hda bing HCI 5% thu dugc tua. Lpc, rira tiia b i n g nudc elt. S l y khd d 70°C thu dugc san p h i m kdt tinh mau tring, Hieu suit: 78,0%;
mp. 176-177°C; Rf = 0,44 (DCM:MeOH:AcOH, 90:10:1), IR (KBr cm''): 3400-2500 (OH acid), 3207 (NH), 1695 (C=0), 1619, 1556, 1457 (C=C), 2953, 2930 (CHj). ESI-MS: m/z 294 [M+H]", 261 [M-NHOH]" 151 [M-CO-(CH2)4- CONHOH+2]" 'H-NMR (500 MHz, DMSO.
ppm)- 6 1,50-1,57 (2H, m, CH2); 1,59-1,65 (2H, m, CH2); 1,96-2,00 (2H, m, CH2); 2,47 ( I H , CH2); 7,29 (1H, t, J = 7,5 Hz, H-5); 7,42 (1H, t, J - 7,5 Hz, H-6); 7,72 ( I H , d, J = 8 Hz, H-7), 7,95 ( I H , 6.J = 7,5 Hz, H-4); 8,66 ( I H , s, NH); 10,35 ( I H , s, NH), 12,27 ( I H , s, OH).
N'-(6-Methylbenzo[d]thiazol-2-yl)-N^-
hydroxyadipamid (3b). Tidn hdnh tuang tu nhu c h i t (3a), c h i t ban d i u phan ung Id methyl 5-(6-methylbenzo[d]thiazol-2-yl carbamoyl) pentanoat, Hieu suit: 78,0%; mp: 204-205°C; R, = 0,48
(DCM:MeOH:AcOH, 90:10:1). IR (KBr cm''):
3400-2400 (OH acid), 3271 (NH), 1707, 1648 (C=0), 1606, 1559, 1471 (C=C), 2952, 2868 (CH2). ESI-MS: m/z 308 [M+H]", 275 [M- NHOH]" 164 [M-CO-(CH2)4-CONHOH + 1]*
'H-NMR (500MHz, DMSO, ppm): 5 1,49-1,62 (4H, m, CH2); 1,96-1,99 (2H, m, CH2); 2,40 (3H, s, CH3); 2,45-2,50 (2H, m, CH2); 7,23 ( I H , d, J = 8,5Hz, H-5); 7,60 ( I H , d, J = 8 Hz, H-4); 7,73 ( I H , s, H-7); 8,65 ( I H , s, NH); 10,35 ( I H , s, NH); 12,19 ( I H , s, OH).
N'-(6-Methoxybenzo[d]thiazol-2-yl)-N^-hydro xyadipamid (3c). Tidn hdnh tuang tu nhu chit (3a), chit ban d i u phan irng la methyl 5-(6- methoxybenzo[d]thiazol-2-yl carbamoyl) pentanoat.
Hieu suit: 84,0%; mp: 189-190°C; R, = 0,41 (DCM MeOH:AcOH, 90:10:1), IR (KBr cm''):
3500-2400 (OH acid), 3250 (NH), 1688 (C=0), 1610, 1562, 1476 (C=C), 2952, 2875 (CH2). ESI- MS: m/z 324 [M+Hf, 291 [M-NHOH]*, 180 [M-CO- (CH2)4-CONHOH+1]" 'H-NMR (500MHz, DMSO, ppm): 5 1,51-1,61 (4H, m, CH2); 1,96-1,99 (2H, m, CH2); 2,44-2,47 (2H, m, CH2); 3,80 (3H, s, OCH3);
7,01 (IH, dd, J = 8,5 Hz, 2,5Hz, H-5); 7,54 (IH, d, J =2,5 Hz, H-7); 7,61 (1H,d, J = 9 H z , H-4).
N'-(6-Ethoxybenzo[d]thiazol-2-yl)-N^-
hydroxyadipamid (3d). Tien hanh tuang tu nhu c h i t (3a), c h i t ban dau phan irng la methyl 5-(6-ethoxybenzo[d]thiazol-2-yl carbamoyl) pentanoat, Hieu suit: 86,0%; mp: 193-194°C; R/
= 0,42 (DCM:MeOH:AcOH, 90:10:1), IR (KBr cm''): 3500-2500 (OH acid), 3252 (NH), 1688 (C=0), 1611, 1560, 1470 (C=C), 2982, 2951 (CH2). ESI-MS: m/z 338 [M+H]\ 194 [M-CO- (CH2)4-CONHOH]* 'H-NMR (500MHz, DMSO, ppm): 5 1,34 (3H, [, J = 7 Hz, CH3); 1,50-1,54 (2H, m, CH2); 1,55-1,61 (2H, m, CH2); 1,96-1,99 (2H, m, CH2); 2,44-2,49 (2H, m, CH2); 4.04-4,08 (2H, m, -OCH2-); 7,0 ( I H , dd, J = 9 Hz, 2,5 Hz, H-5); 7,52 ( I H , 6, J = 2,5 Hz, H-7), 7,60 ( I H , d, J = 9 Hz, H-4); 8,65 (1H, s, NH); 10,35 ( I H , s, NH); 12,13 ( I H , s, OH).
N'-(6-Methylsulfonylbenzo[d]thiazol-2-yl)- t^-hydroxyadipamid (3e). Tien hdnh tuang t u nhu c h i t (3a), c h i t ban dau phan ung la methyl 5-(6-methylsulfonylbenzo[c/]thiazol-2-yl carbamoyl) pentanoat. Hidu suit: 74,0%; mp: 220-221°C, R,
= 0,39 (DCM:MeOH:AcOH, 90:10:1), IR (KBr cm''):
3400-2500 (OH aeid), 3328 (NH), 1698 (C=0), 1604, 1544, 1447 (C=C), 2931 (CH2). ESI-MS: m/z 372 [M+H]' 227 [M-CO-(CH2)4-CONHOHr ' H - NMR (500MHz. DMSO, ppm): 5 1,52-1,57 (2H, m.
TAP CHi DUOC HQC - 7/2011 (SO 423 NAM 51) 57
CH2); 1,59-1,63 (2H, m, CH2); 1,97-2,00 (2H, m, CH2); 2,50-2,54 (2H, m, CH2); 3,23 (3H, s, CH3);
7,90-7,94 (2H, H-4, H-5); 8,62 ( I H , s, H-7); 8,66 ( I H , s, NH); 10,35 (IH, s, NH); 12,60 ( I H , s, OH).
N'-(6-Nitrobenzo[d]thiazol-2-yl)-N^-hydroxya dipamid (3f). Tidn hdnh tuang t u nhu c h i t (3a), c h i t ban d i u phan ung Id methyl 5-(6- nitrobenzo[d]thiazol-2-yl carbamoyl)pentanoat.
Hieu suit: 80,0%; mp: 214-215°C; Rf = 0,39 (DCM:MeOH:AeOH, 90:10:1). IR (KBr cm''):
3400-2400 (OH acid), 3301 (NH), 1706 (C=0), 1644, 1577, 1450 (C=C), 2926 (CH2). ESI-MS:
m/z 339 [M+Hf, 305 [M-NHOH-1]" 196 [[M-CO- (CH2)4-CONHOH+2]* 'H-NMR (500MHz, DMSO, ppm): 5 1,52-1,57 (2H, m, CH2); 1,59- 1,64 (2H, m, CH2); 1,97-2,00 (2H, m, CH2); 2,52- 2,55 (2H, m, CH2); 7,86 ( I H , d, J = 9 Hz, H-5);
8,25 ( I H , d, J = 8 Hz, H-4); 8,66 ( I H , s, H-7);
9,00 (1H,s, NH); 10,35 ( I H , s, NH),
Thip tac dung LFC chd enzym histon deacetylase
Thir tac dung irc chd enzym HDAC duge thue hien tai Khoa Dugc Trudng Dai hpe Chungbuk, Chonju, Hdn Qudc vd Vien nghien euu sinh hpc va cdng nghe sinh hpc Han Qudc (KRIBB). Tae dung uc chd hoat tinh HDAC eua cac d i n c h i t tdng hgp duac ddnh gid gidn tidp thdng qua xac dinh mirc dp acetyl hda histpn H3, H4 trong rVSMCs, Phan tieh dua tren Western blot cd the khdng djnh d u g c tac dung eiia edc m i u thir lam tang hoac giam s u acetyl hda histon H3, H4 khi so sdnh vdi mdu t r i n g ' " '
Thip doc tinh t§ bao in vitro
Thir ddc tinh td bao in vitro duge thue hien tai Khoa Dugc, Trudng dai hpe Chungbuk, Cheongju, Han Qude theo phuang phap da edng bd''^' vd gia tr| IC50 duge tinh theo phuang phap Probit"^'
Ban luan
Phan ung amid hda cae 2-aminpbenzpthiazpl vdi aeid monomethyl adipie dd tao cae d i n c h i t methyl 5-(be_nzo[d]thiazol-2-yl carbamoyl) pentancat thuc hien dd dang, hieu s u i t tuang ddi eao. Tdc nhdn hoat hda nhdm earboxylie la CDI.
Phan irng tao aeid hydroxamic vdi NHjOH.HCI dd thu dugc eac d i n c h i t (3a-f) c i n tidn hdnh d didu kien 0°C de tranh thuy phan ester trung gian do trong phan irng cd mdt NaOH, Phan ung xay ra nhanh khoang 30 phiit ddn 1 gid 30 phut. Hieu s u i t phan ung tuang ddi cao. DO' lieu phd MS, IR va ' H - N M R eho
phdp k h i n g djnh cau true cua san pham 3a-f dung nhu d u kidn.
Sau khi tdng hgp vd k h i n g djnh cau true cua 6 c h i t tdng hgp dugc, ehung tdi da tien hdnh thir tac dung u'c chd HDAC tai Khoa Dugc, Dai hpc Chungbuk vd Vien nghien ciru sinh hpc va edng nghe sinh hpc Han Qudc (KRIBB). Ket qua thir tdc dung u'c chd HDAC d ndng dp 1 ug/ml chp t h i y ed 4 c h i t 3a-d thd hien tac dung irc chd HDAC (bang 1). Tir kdt qua thir tae dung tren enzym HDAC, chimg tdi tidn hanh thii' ddc tinh te bao In vitro tren ddng te bao ung t h u dai trdng SW620. Ket qua thii' ddc tinh cung dugc tdm t i t tren bang 1.
Bang 1: Dpc tinh tren ti bao ung thw dai tring SW620 cua cie chit 3a-f
Hgp chat TD irc che
HDAC IC5o(^g/ml)
3a + 7.85
3b + 4.69
3c + 9.07
3d + 9.26
3e
>30 3f
>30 Ghi chu;"+" = duang tinh;"-" = am tinh
Sd lieu d bang 1 cho thay 4 d i n chat 3a-d cd tac dung manh vdi gia tri IC50 tir 4,69 ddn 9,26 l-ig/ml. Hai c h i t 3e-f khdng gay dde ddi vdi ddng td bdo tren (IC50 > 30 pg/ml). Kdt qua ndy cho t h i y cd mdi tuang quan giu'a hoat tinh irc chd HDAC va ddc tinh td bao va ggi y ire chd HDAC cd the la mdt c a chd tac dung dde td bao cua cdc chat nay.
Cdc kdt qua trdn la c a s d cho cac nghien CU'U tidp theo djnh h u d n g keo dai c l u ndi vd nghien eiru anh hudng cua vdng tham ddn tdc dung ue chd HDAC cung n h u ddc tinh tren te bap ung thu. Cac d i n chat 3a-f cung la nhung d i n c h i t trien vpng chp nghien ciru tidp tdc dung chdng khdi u in vivo.
K§t luan
Nhu vay, chiing tdi da tdng hgp dugc 6 dan chat A/'-(benzp[d]thiazol-2-yl)-//-hydroxyadipamid.
Kdt qua thir hoat tinh sinh hpc cho thay 4 c h i t 3a- d ed tdc dung irc che HDAC tdt cung nhu cd dpc tinh tren td bac ung thu dai trang SW620. Ket qua nay eho t h i y ede d i n c h i t acid hydroxamic mang khung benzothiazol nay cd trien vgng cho nghidn cuu tidp theo n h i m tao ra cdc d i n chat acid hydroxamic mdi (yc che HDAC.
S u m m a r y
A series of N^-(benzo[d]thiazol-2-yl)-f/- hydnDxyadipamide derivatives were synthesized and evaluated for their inhibitory activities on HDAC
58 TAP CHl DUQC HQC - 7/2011 (SO 423 NAM 51)
and cytotoxicities in SW620 cell line as well. The four compounds 3a, 3b, 3c, 3d exhibited potent HDAC and cell proliferation Inhibitory activities on SW620 with ICso values from 4,69 to 9.26 /.g/ml.
Liy\ cam e n
Od tdi duge hoan thdnh nhd mdt phdn kinh phi tu Chuang trinh nghien euu ca ban, Bd Khoa hpc vd Cdng nghe (NAFOSTED) c l p cho TS. Van Thj My Hue vd dd tdi e l p trudng eiia trudng DH Duac Ha Ndi e l p eho ThS. Dao Thi Kim Oanh.
Tai lieu tham khao
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Characterization of the classical HDAC family, Biochem.J., (2003), 370. 737-749.
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B e n h l a o . . . (Tiip theo trang 60)
dae trung cho viem mdng nao do lao man tinh da dugc xde nhan" Dd la chung cd eua ty le ehdt cao d dp tudi thanh nien.
Thd dan Ble My cd le da trai qua dai djch lao.
Phai chdng xay ra dai djch do cdch sdng eua hp, Cdch sdng ehung hdn tap va hun khdi trcng bdp Id eiia nhu'ng cdn nha cd kdo ddi trong mua ddng k h i c nghidt, ed Id dd tao thanh mdt tdc nhdn tao thudn lgi cho s u truyen bdnh nhidm khuan trong khdng khi, Dd Id chua ke tdi each hut thude Id (loai cdy md ngudi phuang Tdy khi dd chua biet tdi).
Theo nha khoa hpc ndi tren, ngudi ta t h i y bdnh lao trdn ngudi t u ngudn gde s u phdt sinh vi khuan lao dd dugc thue hidn ndm 2005 d
Vien Pasteur (Phdp) chung td b$nh x u l t hi$n It n h l t tu 3 trieu ndm trudc.
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Ngudi ta cdn t h i y khuan x o l n d trong ndo ngudi ldn. Hien nay chua the ndi thdi dd dd cd benh giang mai hay chua. Khi tiep xue, ddn tdc da dd thudng bi chet hang loat do cdc bdnh do sidu khuIn (nhu cum, ddu mua); edc bdnh ndy sau dd truyen sang ngudi chdu Au.
Nguyen Khang
(Theo Bdo Khoa hpc vd Tuang Laixudt bdn a Phdp thdng 8-2010)