Tổng hợp và thử tác dụng kháng nấm, kháng khuẩn của các dẫn chất benzothiazol. Phần 7: N-(Benzothiazol-2-yl)-4- nitrobezensulfonamid và dẫn chất

Nghien CLFU - Ky thuat<br /> <br /> Tong hop va thu* tac dung khang nam, khang<br /> khuan cua cac dan chat benzothiazol<br /> Phan 7: A^-(Benzothiazol-2-yl)-4-<br /> m r<br /> nitrobezensulfonamid va dan chat<br /> Phan Thj Phuong Dung, Nguyen Hai Nam<br /> Bo mon Hoa Duac - Trudng DH Duac Ha Noi<br /> <br /> Dat van de Merck hoac Sigma-Aldrich. S i c ky Idp mdng<br /> Cac benzothiazol la mdt nhdm d i n chit Idn vdi tiin hanh tren ban mdng silica gel GF-254. Diem<br /> nhiiu hoat tinh sinh hge dang chu y. Trong khudn chay xac dinh b i n g may do nhiet do ndng ehay<br /> khd chuang trinh nghien eu'U cac d i n chit nhiet dien. Phd hdng ngoai (IR) ghi tren may<br /> benzothiazol hudng hoat tinh khang n i m , khang Perkin-Elmer. Phd khdi lugng (MS) dugc ghi<br /> khuin va khang t i bao ung thu, ehung tdi da tdng tren may khdi phd LC-MS-OBBITRAP-XL<br /> hgp eae d i n chit 2-aeylaminobenzothiazol '^', Thermo SCIENTIFIC-USA theo phuang phap<br /> (benzothiazol-2-yl)eyelopropanearboxamid '^', ESl-MS (Eleetrospray Ionization). Phd edng<br /> (benzothiazol-2-yl)cyclohexancarboxamid '^', 2- hudng tu' proton (^H-NMR) duge ghi tren may<br /> phenylbenzothiazol '^l Tiip tue hudng nghien cuu Bruker AV-500. ;. ,t<br /> nay chiing tdi da tdng hgp day d i n chit N- Tdng hap cac din chit<br /> (benzothiazol-2-yl)-4-nitrobezensulfonamid nhim Cac din chit A/-(benzothiazol-2-yl)-4-<br /> tim kiim eae chit ed hoat tinh sinh hge tiim nang nitrobenzensulfonamid vdi eae nhdm t h i R khac<br /> thugc nhdm cac d i n chit benzothiazol nay. nhau d vi tri sd 6 eua vdng benzothiazol (2a-f)<br /> T h y e nghiem va ket qua va 1 din chit A/-(benzothiazol-2-yl)-4-<br /> Dung mol, hda chit, dung cu aminobenzensulfonamid (3c) duge tdng hgp<br /> Hda chit, dung mdi dugc nhap tu cdng ty theo sg dd ehung sau day:<br /> <br /> -•'^f-Gr^ 2a: R= H<br /> ^ NH, ^ NH/O 2b: R= CH3<br /> 2c: R = OCH3<br /> s la-f<br /> pyridin, 60°<br /> 2a-f %<br /> SnCl2<br /> v/ NO, 2d:<br /> 2e:<br /> 2f:<br /> R =<br /> R =<br /> R =<br /> OC2H5<br /> SO2CH3<br /> NO2<br /> <br /> ir EtOH<br /> <br /> ^<br /> NH2 3c: R = OCH3<br /> 3c o \ /<br /> <br /> N-(Benzothiazol-2-yl)^nitrobenzensulfonamid (2a): dung s i c ky Idp mdng vdi he dung mdi (DCM:<br /> (Phuang phap A). Hoa tan 300 mg (~2 mmol) 2- MeOH = 13: 01) d i kiem tra tiin trien phan u'ng.<br /> aminobenzothiazol (1a) trong binh c i u day trdn Sau khi k i t thue phan u'ng them 20 ml dung dich<br /> dung tich 50ml bing 4 ml pyridin. Vira khuiy NaHCOa 5% vao binh, l i c d i u va de lanh trong<br /> vira them tir tu* 528 mg (-2,4 mmol) 4- khoang 10 phut Lge qua giiy Ige khdng g i p<br /> nitrobenzensulfonylclorid. Thuc hien eae thao n i p de liy tua. Ru'a tua bing 20 ml dung dich<br /> tae nay trong tu hdt. De phan u'ng ehay trong HCI 5%. Rira lai tua bing nude cit. Kiem tra dp<br /> 18-24h d nhiet do 60°C tren may khuiy tir. Sir tinh khiit cua san p h i m bing s i c ky Idp mdng<br /> <br /> <br /> 24 TAP CHI DirpC HOC - 12/2010 (SO 416 NAM 50)<br />  Nghien CLFU - Ky thuat<br /> (hda tan trong DCM hoac aceton) vdi he dung ESl-MS, 378 [M-H]", (M=379). ^H-NMR (500MHz.<br /> mdi tren. S i y san pham thu dwac a nhiet do DMSO), 5 (ppm): 8,37 ( dd, 2H, J, = 2,0 Hz; J2 = 7,0<br /> 60°C d i n khd. Hieu suit 74,0 %; t V = 229,6- Hz , H-3', H-5'); 8,08 (dd, 2H, Ji = 2,25 Hz; J2 = 9,25<br /> 230,4°C; IR (KBr, em"^): 3109 (VN-H); 3038/2906 Hz, H-2', H-6'); 7,47 (d, IH, J = 2,5 Hz, H-7); 7,24<br /> (VC-H); 1603 (VC=N); 1544/1524/1464/1398 (vc=c); (d, 1H, J = 9,0 Hz, H-4); 6,99 (dd, IH, Ji = 2,5 Hz;<br /> 1349/1337/1150 (Vgoa); 1261/962 (VC-N); 853/832 J2 = 9,0 Hz , H-5); 4,02 (m, 2H, O-CH2-CH3); 1,31<br /> (vc-N ArNoa). ESI-IVIS [m/z): 366 [M-H]", 186 (dd, 3H, Ji = 6,75 Hz; J2 = 13,75 Hz, O-CH2-CH3)<br /> [S02C6H4N02r, 122 [C6H4N02]^ (M=335). ^H-NMR N-[(6-Methylsulfonyl-benzothiazol)-2-yl]-4-nitro<br /> (500MHz, DMSO), 5 [ppm): 8,37 (d, 2H, J = 9,0 Hz, benzensulfonamid (2e): theo phuang phap A,<br /> H-3', H-5'); 8,11 (d, 2H, J = 8,5 Hz, H-2', H-6'); 7,83 thay 2 mmol 2-aminobenzothiazol (la) bing 2<br /> (d, 2H, J = 8,0 Hz, H-4); 7,41 (td, IH, Ji = 0,83 Hz; mmol 2-amino-6-methylsulfonylbenzothiazol (le).<br /> J2 = 7,75 Hz, H-5); 7,34 (d, 1H, J = 7,5 Hz, H-7); Hieu suit 50%; t V = 117,2-117,9°C; IR (KBr, cm"'):<br /> 7,29 (td, IH, Ji = 1,0 Hz; J2 = 8,0 Hz, H-6). 3372 (VN-H); 3017/2931 (VOH); 1604 (VC=N);<br /> N-[(6-Methylbenzothiazol)-2-yl]-4-nitrobenzen 1529/1461/1444 (vc=c); 1347/1157 (VS02); 1284/966<br /> sulfonamid (Zbj. Theo phuang phap A, thay 2 (VC-N); 852 (VC.NA^02). ESl-MS {m/z): 412 ([M-H]"-1),<br /> mmol 2-aminobenzothiazol (1a) bing 2 mmol 2- (413); ^H-NMR (500MHz, DMSO), 5 (ppm): 8,27 (d,<br /> amino-6-methylbenzothiazol ( l b ) Hieu suit 64,0 2H, J = 9,0 Hz, H-3', H-5'); 8,10 (d, IH, J = 1,5 Hz,<br /> %; t°nc = 243,1-243,5°C; IR (KBr, em"^): 3103 (VN-H); H-7); 8,04 (d, 2H, J = 8,5 Hz, H-2', H-6'); 7,62 (dd,<br /> 3038/2900 (VC-H); 1609 (VC=N); 1596/1548/1538 IH, Ji = 1,75 Hz; J2 = 8,25 Hz , H-5); 7,42 (d, IH, J<br /> (Vc=c); 1348/1336/1152 (VS02); 1263/963 (VQ-N); 855 = 8,5 Hz, H-4); 3,13 (s, 3H, SO2CH3).<br /> (VC-N ArN02). ESl-MS (m/z): 350 [M+H]*, 227 ([M- N-[(6-Nitrobenzothiazol)-2-yl]-4-nitrobenzen<br /> C6H4N02r-1), 165 [M-S02C6H4N02+Hr, 150 [M- sulfonamid (li): theo phuang phap A, thay 2<br /> NHS02C6H4N02+Hr, 122 [C6H4N02r, ( M = 3 6 5 ) . ' H - mmol 2-aminobenzothiazol (1a) bing 2 mmol 2-<br /> NMR (500MHz, DMSO), 5 (ppm): 13,40 (brs, IH, amino-6-methylsulfonylbenzothiazol (If). Hieu<br /> NH); 8,37 (d, 2H, J = 9,0 Hz, H-3', H-5'); 8,10 (d, 2H, suit 55,0%; t°nc = 239,6-240,5°C; IR (KBr, cm"''):<br /> J = 8,5 Hz, H-2', H-6'); 7,64 (brs, IH, H-5); 7,23 (brs, 3136 (VN-H); 1608(VC=N); 1554/1533/1521 (vc=c);<br /> 2H, H^, H-7); 2,34 (s, 3H, CH3). 1349/1151 (VS02); 13449 (VN=O); 960 (VQ-N); 1066<br /> N-[(6-Methoxybenzothiazol)-2-yl]-4-nitrobenzen (Vc-o-c); 847 (Vc-NArN02). )• ESl-MS (m/z): 379 [M-<br /> sulfonamid f2c|- theo phuang phap A thay 2 H]", 202 [NHSO2C6H4NO2-H]", 193 [M-<br /> mmol 2-aminobenzothiazol (la) bing 2 mmol 2- SO2C6H4NO2-H]", (380); ^H-NMR (500MHz,<br /> amino-6-methoxybenzothiazol (1c). Hieu suit DMSO), 5 (ppm): 8,86 (brs, 1H, H-7); 8,38 (d, 2H,<br /> 60,0 %; t°nc = 213,9-214,2°C; IR (KBr, cm"''): J = 8,5 Hz, H-3', H-5'); 8,26 (dd, IH, Ji = 1,5 Hz; J2<br /> 3106 (VN-H); 3039/2988 (VC-H); 1593 (VC=N); = 8,25 Hz, H-5); 8,12 (d, 2H, J = 8,5 Hz, H-2', H-<br /> 1552/1520/1486 (vc=c); 1349/1331/1150 (Vgoz); 6'); 7,47 (d, IH, J = 9,0 Hz, H^); ^^C-NMR (125<br /> 1271/965 (Vc-N ); 1068 (Vc-o-c); 853 (VC-N ArN02). MHz, DMSO, ppm): 5 169,5^ (C-2); 149,61 (C-<br /> ESl-MS (m/z): 366 [M+H]\ 181 ([M-SO2C-6H- 9); 146,92 (C-4'); 143,15 (C-1'); 142,59 (C-6);<br /> 4N02+Hf+1), 165 [M-NHS02C6H4N02+Hr, 122 127,47 (C-2', C-6'); 126,66 (C-8); 124,58 (C-3',<br /> [C5H4N02]^ (M=365).'H-A/yWR (500MHz, DMSO), 5 C-5'); 123,23 (C-4); 119,31 (C-5); 113,52 (C-7).<br /> ippm): 8,37 (d, 2H, J = 9,0 Hz, H-3', H-5'); 8,09 (d, N-[(6-Methoxybenzothiazol)-2-yl]-4-aminobenzen<br /> 2H, J =. 9,0 Hz, H-2', H-6'); 7,48 (d, IH, J = 2,0 Hz, sulfonamid (3c) (Phuang phap B): Dun hdi luu<br /> H-7); 7,25 (d, IH, J = 9,0 Hz, H^); 7,00 (dd, IH, Ji trong 30 phiit hdn hgp gdm 730 mg (~ 2 mmol)<br /> = 2,5 Hz; J2 = 9,0 Hz , H-5); 3,76 (s, 3H, OCH3). N-[(6-methoxybenzothiazol)-2-yl]-4-nitrobenzen<br /> N-[(6-Ethoxy-benzothiazol)-2-yl]-4-nitrobenzen sulfonamid (2c), 4,6g (~ 20 mmol) SnCl2.2H20,<br /> sulfonamid (•2dj; theo phuang phap A, thay 2 1,5 ml HCI dac va 15 ml edn 96° trong binh c i u<br /> mmol 2-aminobenzothiazol (la) bing 2 mmol 2- 50 ml tren may khuiy tu-. Kiem tra tiin trien<br /> amino-6-ethoxybenzothiazol (Id). Hieu suit phan irng bing s i c ky Idp mdng vdi he dung<br /> 40,0%; t°nc = 213,7-214,7°C; IR (KBr, cm"^): 3107 mdi DCM : methanol = 9:1. Sau khi k i t thuc<br /> (VN-H); 3051/2987/2932 (VC-H); 1591 (VC=N); phan U'ng, c i t quay loai bdt ethanol. K i i m hda<br /> 1552/1520/1488 (Vc=c); 1350/1152 (vso2); hdn hgp thu dugc bing NaOH 10%i d i n pH = 4.<br /> 1271/966 (VC-N); 1066 (vc-o-c); 851 (VC-N ArN02). Chiit l i y san pham tu" hdn hgp tren bing 20 ml<br /> <br /> <br /> TAP CHI DUOC HOC - 12/2010 (SO 416 NAM 50) 25<br />  Nghien CLFU - Ky thuat<br /> ethylaeetat x 2 l i n . Lam sach dich chiit tiin hanh trong mdi trudng khan nude. Pyridin<br /> ethylaeetat vdi 20 ml NaCI bao hda. Lge djeh dugc diing trong phan irng amid hda vdi ba<br /> chiit qua phiu ed Na2S04 khan. Cd bdt muc dich: lam dung mdi hda tan cae 2-<br /> ethylaeetat d i n khi xuit hien tua. De lanh qua aminobenzothiazol; xue tae cho phan irng N-<br /> dem. Lge liy tua va rira tua bing n-hexan lanh. aeyl hda; h i p thu HCI sinh ra trong phan irng.<br /> Siy d 70°C d i n khd. Hieu suit 17%; t°nc = 240,2- Trong phan u'ng nay, 4-nitrobenzensulfonylelorid<br /> 241,8°C; IR (KBr, cm"'): 3491/3461/3375/3364(VNH2); duge dung du d i dam bao cae nguyen lieu ban<br /> 3109 (VN-H); 3051/2954/2922/ 2851 (VC-H); 1596 d i u 2-aminobenzothiazol (1) phan u'ng h i t , giiip<br /> (VC=N); 1552/1503/1487 (Vc=c); 1312/1289 (Vso2); eho viee tinh c h i san p h i m duge d i dang.<br /> . 1271/956 (VC-N); 1086/1063 (Vc-o-c). ESl-MS Phan U'ng khir hda dung d i chuyen nhdm<br /> (m/z): 336 [M+H]*, (M=335). ^H-NMR (500MHz, nitro eua hgp chit 2c thanh hgp c h i t amin 3c-<br /> DMSO), 5 (ppm): 12,71 (s, IH, NH); 7,47 (dd, 2H, vdi tae nhan la SnCl2. Mae du phan irng nay<br /> J, = 2,0 Hz; J2 = 7,0 Hz , H-3', H-5'); 7,41 (d, IH, J thue hien trong thdi gian ngin (15 phut) nhung<br /> = 2,5 Hz, H-4); 7,17 (d, IH, J = 4,5 Hz, H-7); 6,95 do cd the xay ra ddng thdi phan u'ng phu thuy<br /> (dd, IH, Ji = 2,5 Hz; J2 = 9,0 Hz, H-5); 6,58 (dd, phan chirc sulfonamid eua nguyen lieu 2c, them<br /> 2H, Ji = 1,75 Hz; J2 = 6,75 Hz, H-2', H-6'); 5,87 (s, nira qua trinh xit ly san p h i m phirc tap nen hieu<br /> 2H, -NH2); 3,57 (s, 3H, -OCH3). suit phan irng thu duge khdng eao (17-56%).<br /> ThiF hoat tinh khang k h u i n , khang n i m : Cae san p h i m dirac khing djnh ed c i u triic<br /> Hoat tinh khang khuin, khang n i m in vitro phii hgp vdi c i u true d y kiin thdng qua k i t qua<br /> duge thu tren phiin vi lugng 96 Id theo phuang phan tich phd IR, phd MS va phd ^H-NMR. Phd<br /> phap da dugc cdng bd '''' tai Phdng sinh hgc thue IR ciia ca 7 c h i t tdng hgp duge d i u xuit hien<br /> nghiem - Vien Hda hge cae hgp chit thien nhien dai h i p thu n i m trong khoang 3103-3372 cm'^<br /> thude Vien Khoa hge va Cdng nghe Viet Nam. Cac dae trung cho dao dgng hda trj cua nhdm -NH<br /> ehung vi sinh vat kiim dinh gdm: 2 chiing vi khuin ed trong phan t u eae c h i t Dai h i p thu nim<br /> gram (-): Escherichia coll, Pseudomonas trong khoang 1350- 1347 cm'^ dae trung cho<br /> aeruginosa; 2 ehung vi khuin gram (+): Bacillus dao ddng hda trj ddi xu'ng cua nhdm -SO2 trong<br /> subtilis, Staphylococcus aureus; 2 ehung n i m sgi: nhdm chire sulfonamid. Ngoai ra, sau khi khu'<br /> Aspergillus niger, Fusarium oxysporum; 2 chiing nhdm NO2 tham d c h i t 2c, tren phd hdng ngoai<br /> n i m men: Candida albicans, Saccharomyces eiia chit 3c ed x u i t hien dai h i p thu d khoang<br /> cerevisiae. Miu chit tinh khiit cd MIC < 50 |j.g/ml 3491-3364cm"^dac trung cho dao dgng hda trj<br /> duge coi la chit ed hoat tinh. cua nhdm NH2 tham. Phd E 6 | - M S cua 7 chit<br /> Ban luan d i u cd pic phan tir cd sd khdi dung bing sd khdi<br /> dy kiin, phd dd cho phep nhan biit cae pic<br /> Tdng hccp hda hoc va xac djnh c i u true<br /> phan manh phu hgp vdi sa dd phan manh eua<br /> Chung tdi da tdng hgp duge 7 d i n c h i t<br /> eae chit. Phd edng hudng tu- hat nhan ' ' H - N M R<br /> benzothiazol thdng qua 2 loai phan irng amid<br /> eho gia trj do chuyen djeh hda hgc tuang irng<br /> hda va khir hda.<br /> vdi eae proton trong cac khung benzothiazol,<br /> Phan U'ng amid hda dugc sir dung d i tdng khung phenyl va cua cac nhdm t h i d vj tri sd 6<br /> hgp eae d i n chit 2a-2f. Day la phan u'ng xay ra tren vdng benzothiazol.<br /> kha d i dang trong thdi gian ngin vdi hieu suit<br /> trung binh tir 40-70%. Tac nhan aeyl hda trong NH O<br /> cac phan irng la 4-nitrobenzensulfonylelorid d§ \//<br /> RV<br /> bj phan huy khi gap i m nen cac phan u'ng dugc<br /> Bang 1: Kit qua thir hoat tinh khang khuin, khang nim<br /> \y<br /> Nong do u'c che toi thieu (MIC:pg/ml)<br /> TT Chat RI R2 VK Gr(-) VK Gr(+) Nam moc Nam men<br /> EC PA BS SA AN FO SC CA<br /> 1 2a H NO2 50 - - - -<br /> 2 2b CH3 NO2 - - - - -<br /> 3 2c OCH3 NO2 50 - 25 - -<br /> <br /> 26 TAP CHI DLTOC H O C - 12/2010 (SO 416 NAM ?0)<br /> • Nghien CLFU - Ky thuat<br /> Nong do ire che toi thieu (MIC:pg/ml)<br /> TT Chat R1 R2 VK Gr(-) VK Gr(+) Nam moc Nam men<br /> EC PA BS SA AN FO SC CA<br /> 4 2d OC2H5 NO2 50 - - -<br /> 5 2e NO2 NO2 50 - 50 -<br /> 6 2f SO2CH3 NO2 - - - -<br /> 7 3c OCH3 NH2 - - - -<br /> Ghi chu: EC, Escherichia coli; PA, Pseudomonas aeruginosa; BS, Bacillus subtillis; SA, Staphyloccocus<br /> SC, Saccharomyces cerevisiae; CA, Candida albicans.<br /> aureus; AN, Aspergillus niger; FO, Fusarium oxysporum;<br /> Tac dung sinh hoc - tae dung sinh hgc cua day d i n chit nay.<br /> Chiing tdi da thu sa bd hoat tinh khang n i m , + So sanh day 2(a-g) vdi day N-(benzothiazol-<br /> khang khuan ciia ca 7 chit gdm 2(a-e) va 3c 2-yl)cyclopropancarboxamid (4a-f) '^' va N-<br /> tren 8 chiing vi sinh vat cua Phdng sinh hge (benzothiazol-2-yl)cyelohexancarboxamid (5a-f) '^'<br /> thye nghiem - Vien Hda hge cac hgp chit thien ma chiing tdi da tdng hgp va thir hoat tinh trudc<br /> nhien thude Vien Khoa hge va Cdng nghe Viet dd thi cac d i n chit thugc day 4 va 5 cd tac dung<br /> Nam va riit ra mdt sd nhan xet sau: khang khuin, khang n i m rdng va manh han: nam<br /> + Cd 4 chit cd tac dung tren it nhit mgt chiing trong bay chit cua day 4 cd tae dung khang<br /> vi sinh vat thir nghiem, trong dd 2 chit 2a, 2d ed khuin, khang nim; h i u h i t cae chit d i u cd tac<br /> hoat tinh tren chiing vi khuin Escherichia coli; 2 dung tren chiing vi khuin Gr (+) Staphylococcus<br /> chit 2c, 2e cd hoat tinh tren hai ehung vi khuin aureus va chiing n i m mdc Aspergillus niger Dae<br /> Escherichia coll va Staphyloccocus aureus. Chit biet khi nhdm t h i Ri eiia day 4 la amino thi phd<br /> 2c vdi nhdm t h i methoxy d vj tri sd 6 tren khung tac dung duge md rdng han h i n (ed tac dung tren<br /> benzothiazol cd tae dung khang khuin manh nhit 5 ehung vi sinh vat kiem djnh: Pseudomonas<br /> trong day chit. Cd 3 chit 2b, 2f, 3c hoan toan aeruginosa. Bacillus subtilis, Staphyloccocus<br /> khdng cd tae dung tren ca 8 chiing vi sinh vat thu' aureus, Aspergillus niger va Fusarium<br /> nghiem. Ca 7 chit d i u khdng ed tac dung tren cae oxysporum). Ddi vdi day 5 thi cd 4 trong 7 chit ed<br /> ehung vi nim. Do eae chit cd hoat tinh khang tae dung, trong dd chit g i n nhdm t h i OCH3 tai Ri<br /> khuin, khang nim khdng dang ke nen ehung tdi cd tae dung tren 3 chiing vi sinh vat Escherichia<br /> chua thiy duge mdi lien he rd rang giira c i u triie coll, Staphyloccocus aureus, Aspergillus niger<br /> <br /> <br /> <br /> NH 0<br /> "V >-„„ \<br /> -^ ^ 3-<br /> 2(a-f) \ // 4(a-g) // 5(a-g)<br /> <br /> a: R, = H R, = OC2H5 g: R, = NH2<br /> b:Ri = CH3 Ri = SO2CH3<br /> c: R, = OCH3 R, = NO2<br /> <br /> f; Nhu vay ed t h i thiy nhdm chu'c sulfonamid mau, nhung eung khdng qua than d i u de khdng<br /> khdng cd vai trd quan trgng trong hoat tinh bi giu' lai nhiiu d cac md md. Tuy nhien, ehung<br /> khang khuin, khang n i m ciia benzothiazol. tdi chua rut ra duge mdi quan he giO'a tae dung<br /> De sa bd danh gia mdi lien quan giO'a hoat sinh hge vdi gia trj logP cua eae c h i t eu the.<br /> tinh sinh hge va chi sd hda ly cua eae chit, Bang 2: Gia trj logP cua cac chit<br /> Chung tdi da tiin hanh tinh gia trj he sd phan bd Chat Ri R2 logP Chat Ri R2 logP<br /> oetanol - nude (logP) eiia cac chit tdng hgp<br /> 2a -H -NO2 2,63 2e -SO2CH3-NO2 1,19<br /> dugc bing phin m i m KowWin (bang 2). Ddi<br /> vdi chit dung lam thude, logP thudng < 5; tire la 2b -CH3 -NO2 3,17 2f - NO2 -NO2 2,44<br /> du than nude d i tan trong eae dich eua ea t h i 2c -OCH3 -NO2 2,71 3c -OCH3 -NH2 1,97<br /> (da day, rudt, mau), du than d i u d i qua duge<br /> 2d -OC2H5-NO2 3,19<br /> mang t i bao niem mac dudng tieu hda vao<br /> <br /> <br /> TAP CHI DUOC HOC - 12/2010 (SO 416 NAM 50) 27<br />  Nghien CLFU - Ky thuat<br /> Ket luan only marginal Inhibitory effects against 8 strains<br /> Chung tdi da tdng hgp dugc 7 c h i t gdm 6 of fungi and bacteria tested.<br /> d i n chit A/-(benzothiazol-2-yl)-4-nitrobenzen Tai lieu tham khao<br /> sulfonamid va 1 d i n c h i t A/-(6-methoxybenzo 1. Nguyin Hai Nam, Phan Thi Phuo'ng Dung, Dao<br /> thiazol-2-yl)-4-aminobenzensulfonamid. K i t qua Thi Kim Oanh, Tran Phuong Thao, Nguyin Anh<br /> thir hoat tinh khang khuin, khang n i m eho thiy Ngoc. Tong hgp va tac dung sinh hoc cua d i n chit<br /> benzothiazol. P h i n 1: Cac 2-acylaminobenzothiazol,<br /> ed 4 trong 7 chit (2a, 2d, 2c, 2e) ed hoat tinh<br /> Tap chi Dwac hgc s6 12/2008, 392, 12, 31-35.<br /> khang khuan, khang n i m ; c h i t 2c the hien hoat<br /> 2. Phan Thj Phuo'ng Dung, T r i n Phuccng Thao,<br /> tinh tdt nhit khang duge 2/8 chiing VSV kiem<br /> Nguyin Hai Nam. T6ng hgp va tac dung sinh hoc cua<br /> djnh la Escherichia coli, Staphylococcus aureus d i n c h i t benzothiazol. Phan 2. Cac benzothiazol-2-yl-<br /> vdi gia trj MIC tuang u'ng la 50, 25 pg/ml. cyclopropylcarboxamid, Tap chi Dwac hgc s6 2/2009,<br /> Ld"! c a m c n 394, 2, 29-33.<br /> 3. Phan Thi Phuo'ng Dung, T r i n Phuo'ng Thao,<br /> D i tai duge hoan thanh nhd mgt phin kinh<br /> Nguyin Hai Nam. Tong hgp va tac dung sinh hoc cua<br /> phi tu' Chuang trinh nghien eiru ea ban, Bd dan c h i t 2-phenylbenzothiazol, Tap chi Dwac hgc so<br /> Khoa hge va Cdng nghe (NAFOSTED) c i p ehe 5/2009, 397, 43-47.<br /> PGS. TS. Nguyin Hai Nam. 4. Larry M, Kandel J. Microbiology: Essentials and<br /> Summary Applications. Inc New York. 1996.<br /> A senes of N-(benzothiazol-2-yl)-4- 5. Thao TP, Dung PTP, Nam NH. Design,<br /> synthesis and bioevaluation of several series of new<br /> nitrobenzenesulfonamlds and N-(benzothiazol- 2-acylbenzothiazol derivatives - Pharma Indochina VI<br /> 2-yl)-4-aminobenzenesulfonamld were - The development of Indochina pharmacy in the<br /> synthesized and evaluated for antifungal and context of global economic recession - Hue.<br /> antibacterial activities. All compounds exhibited 12/2009,172-177.<br /> <br /> <br /> <br /> > r<br /> <br /> Biro'c dau nghien cmi moi quan he dinh lu'ong<br /> r r<br /> <br /> giua can triic va tac dung doc tinh te bao cua<br /> ft r f<br /> <br /> cac dan chatflavonolvaflavanontong hop<br /> Thai Khac Minh\ Hoang Thi Kim Dung^<br /> 'BO mon Hoa Duac - Khoa Duac - Dai hoc YDuac TP. Hd Chi Minh<br /> ' Vien Cong nghe Hoa hoc - Vien Khoa hoc va Cong nghe VN<br /> <br /> Dat van de Phu'O'ng phap nghien CLPU<br /> Mgt sd nghien eu'U cho thiy cac flavonoid ty ThCp nghiem doc tinh t§ bao tren dong t l<br /> nhien va tdng hgp cd kha nang chdng ung thu bao ung thip v u MCF-7<br /> theo mgt sd ca c h i trgng dd cd chdng sy tang Phugng phap Sulforhodamine B (SRB) dung<br /> sinh hay ngan chan sy phat trien cua t i bao de danh gia kha nang gay doe t i bao ciia tac<br /> (gay dgc t i bao)'^'. Trong nghien eu'U nay, vdi nhan nghien eu'U. Thu" nghiem dya vao kha<br /> mue dich tim ra cae d i n chit ed hoat tinh khang nang eua SRB, la thude nhudm aminoxanthene<br /> ung thu manh han, 11 d i n c h i t flavonol va mau hdng sang vdi hai nhdm sulfonic g i n tTnh<br /> flavanon dugc tiin hanh tdng hgp'^' va thCr dien vdi protein eiia cac t i bao sau khi 6\ygc ed<br /> nghiem hoat tinh doe tinh tren ddng t i bao ung djnh bing TCA. T i bao 6uac nudi trong dTa 96<br /> thu vu MCF-7. Tren ea s d dd, mdi quan he djnh giing. Sau khi ii 24 gid, t i bao duge xii' ly vdi<br /> lugng giO'a c i u true hda hgc va ddc tinh te bao thude d nhO'ng ndng do khae nhau trong 48 gid.<br /> (QSAR) duge xay dyng. Sau dd, t i bao dugc cd djnh b i n g TCA 50% va<br /> <br /> <br /> 28 TAP CHi DirpC HOC - 12/2010 (SO 416 NAM 50)<br />