Tổng hợp và thăm dò tác dụng sinh học của 5(mnnitro benzyliden) Thiazolidin2,4dio và dẫn chất

B Y T TRNG I HC O Dc H NI NGUYN TH THU PHNG TNG HP V THM Dề TC DNG SINH HC CA 5-(m-NITRO BENZYLIDEN) THIAZOLIDIN-2,4-DION V DAN CHAT (KHO LUN T T NGHIP D c S I HC KHO 52 /1997-2002) Ngi hng dn ; TS NGễ TH MAI ANH : THS INH TH THANH Ni thc hin ; B MN HO HU c Thi gian thc hin : 02/03/2002 N 20/05/2002 HI LI CM N ~ C r o v \C ta nkỗm qu i a I v ớn h + k c ki^A l< K o g iỳ p s t h s c lu ỗ m , hn fm k em ca x s A ' g ụ X k ]v\a\ y \ n h , T K S ỡkvK T K T k c m h f-l a i /Kjkv c k o e.m f u c d k \K Kvhrvg dũkA0 a u tik\ t t y d e b y lo I K ỡ< (y \l\ i r v \ g túi s g i u p cf to lcớkỡ v b i t ia s a u s a c , 1.2000 _ MM : 200.00 -> Baseline Erase UieuRe-scale 2oom Label More Use the graphics cursor, track, slope _ 500.00 Hinh 7: Pho tir ngoai cỹa chat II ABS ABS ABS 0.63464 0.460 54 0.72753 NM NM NM 318.000 277.000 241.000 OQ OQ OQ X1 MauIII/"Ph.EtOH Gain 93 ABS _ Basel ine _ OFF 16 Apr 2002 r n n 2.0 J C J D tJCJ fln SBU Page DISPLAY DATA 1.2000 0.8008, / O UĩOO 200 I i i i i / i i \ \ \ V x\ * ! in CD 0.4000- * 300.00 ABS : 0.0000 -> 1.2000 Baseline Erase View Be-scale 2oom Use the graphics cursor, track, s 1ope i MM SẻT57ẻẻ i 400.00 i : 200.00 -> Label More Hinh 8: Pho tu ngoai cua chat III 500.00 500.00 ABS ABS 1.05095 1.53924 - 0 ABS _ NM NM 317.000 249.000 MauW/Ph EtOH/HCo 93 SBW Gain OFF Page Basel ine 16 Apr 2002 2.0 0 0 NH DISPLAY DATA 2.0000 1.6000 1.2000 0.8000 0.4000-1 CJCJ I 0.0000 200.00 400.00 300.00 2.0000 0.0000 ABS Baseline Erase Uieu Re-scale 2oom Use the graphics cursor, track, slope ABS ABS ABS 0.62444 0.44623 0.78605 0.0021 ABS NM NM NM _ m MauU/Ph.EtOH/HCo Gain 93 Basel ine OFF SBU Page : 200-00 Label 317.000 277.000 237.000 500.00 -> 500.00 flore Hinh 9: Pho tu ngoai cua chat IV 16 Apr 2002 2.0 0 0 MM DISPLAY DATA 1.0000 0.8000 0.6000- A \ / 0.4000- 2000 0000200.00 T nr 300.00 ABS :0.0000 -> 1.0000 MU Baseline Erase Uieu Re-scale 2oom Jursor Use the graphics cursor, track, slope _ 400.00 T 500.00 : 200.00 r> 500.00 _ Label More Hinh 10: Pho tÊr ngoai cua chat V ABS ABS ABS 0.25638 0.25958 1.44200 - 0 0 ABS NM NM NM 307.778 274.444 233.333 MauVI -Phuong/Hco Gain 93 SBU Baseline OFF Page 16 Apr 2002 2.0 0 0 _ NM DISPLAY DATA 2.0000 1.6000 1.2000 0.8000- J \ 0.4000- IU(j[ -0.00002 0 R0 I 300.00 I J 400.00 ABS _: 0.0000 -> 2.0000 Base line Erase Use the graphics cursor, track, slope 500.00 _ MM : 200.00 -> 500.00 Uiew Re-scale ZoomLabelMore Hinh 11 : Pho tu ngoai cua chọt VI ABS ABS 29558 49948 R flfln ệ ệ ệ J NM NM 319.000 249 000 MauWT'Ph.EtOH/HCo Gain 93 SBU 16 Apr 2002 2.0 r m o D ệ O -ABS _: 0.0000 -> 0.6000 MM : 200.00 -> Base 1ine Erase Uieiu Re-scale Zoom lifflSfW Label More Use the graphics cursor, track, slope _ Hinh 12: Pho tur ngoai cua chat VII n o ĩ 500 00 [...]... *5-(m- nitro benzyliden)- thiazolidin-2,4-dion (II) *3-(anilino mcthyl)-5-(m-nitro benzyliden)- thiazolidin-2,4-dion (III) *3-(p-lỡuoro anilino methyl)-5-(m-nitro benzyliden)- thia/lidin-2,4-dion (IV) *3-(p-cloro anilino methyl)-5-(m-nitro benzyliden)- thiazolidin-2,4-dion (V) *3-(o-cloro anilino methyl)-5-(m-nitro benzyliden)- thiazolidin-2,4-dion (VI) *3-(p-bromo anilino methyl)-5-(m-nitro benzyliden)- thiazolidin-2,4-dion... bng kh nng c ch s phỏt trin ca vi sinh vt kim nh, to thnh vũng vụ khun cú ng kớnh t l thun vi logarit nng cht th 2.4.1 Cht th Cht th bao gm 6 cht (II- VII) c pha nng 4mg/ml, dung mụi DMF, mu chng l thiazolidin-2,4-dion, móu trng l DMF 2.4.2 Vi sinh vt kim nh Cỏc vi sinh vt dựng trong nghiờn cu l chng quc t v mt s chng c phõn lp Vit Nam nhn c t Vin Kim nghim, Vin V sinh dch t, B Y t Cỏc chng m chỳng... t ngoi ca cỏc cht tng hp do cu trỳc cú cha cỏc h liờn hp K-n ( >C=C-C=0, nhõn benzen ) -max 233- 277 nm ng vi s dch chuyn TC-n* Xmax 307- 318 nm ng vi s dch chuyn n- Tớ* 27 2.4 Th tỏc dng sinh hc ỏnh giỏ hot tớnh sinh hc ca cỏc cht tng hp c vi hy vng tỡm thy cỏc dón cht mi ca thiazolidin- 2,4- dion cú hoi lớnh khỏng khun v khỏng nm, chỳng tụi ó tin hnh th tỏc dng khỏng khun, khỏng nm ti phũng thớ nghim... cỏch cho cht (II) tỏc rớg vi ibrmalehyd v amin thm *Phng trỡnh phn ng: Cl - ỳ ^ 0 ^ Br VII Tt c cỏc phn ng u tin hnh trong mụi trng ethanol, nhit 75- 80c 2.2.4.1 Tng hp 3-(anilino methyl)-5-(m-nitro benzyliden)- thiazolidin-2,4dion (III) *Cụng thc: C17 H13 O4N3 S; M=355 *Tin hnh: Trong bỡnh cu 100 ml, cho vo ú 0,63g (0,0025 mol) cht (il), 15 ml ethanol, va khuy va un nh cho tan Cho tip 0,28 ml (0,00275... núng chy: 129-130,5c tan: Khú tan trong nc, tan ớt trong elhanol, methanol nhit phũng, d tan trong ethanol, methanol núng, accton, cloroform, DMF 2.2A.2 Tng hp 3-(p-fluoro anilino methyl)-5-(m-nitro benzyliden) thiazolidin-2,4-dion (IV) *Cụng thc: N 02 C 17 H12 O4N3 SF; M=373 *Tin hnh: nh 2.2.4.1, nhng thi gian phn ng l 2 gi Hn hp phn ng gm 0,63g (0,0025 mol) cht (II), 0,27 ml (0,00275 mol) p-Fluoro... núng chy: 150- 151,5c 19 tan: Khú tan trong nc, tan ớt trong ethanol, methanol nhit phũng, d tan trong ethanol, methanol núng, aceton, cloroform, DMF 2.2A.3 Tng hp 3-(p-cloro anilino methyl)-5-(m-ntro benzyliden)- thiazoldin-2,4-dion (V) *Cụng thc: N02 C17 PO4N3 SCI; M- 389,5 *Tiờn hnh : nh 2.2.4.1, nhng thi gian phn ng l 2 gi Hn hp phn ng gm 0,63g (0,0025 mol) cht (II), 0,352g (0,00275 mol) p-cloro... (CH3COONa) p-cloro an il in Cn tuyt i (ElOH) o-cloro anilin Methanol (MeOH) p-fluoro anilin Clorolorm (CHCI3) Dimethyl 1o rmami (DMF) Formaldehyd (HCHO) 2.1.2 Phng tin - Bỡnh ha c (V=100ml,500ml,1000ml), sinh hn hi lu, nhit k, mỏy khuy t 13 - Sc ký lp mng (SKLM) c tin hnh trờn bn mng Kieselgel 60 F254 (Merck) - Nhit núng chy o trờn mỏy Variable Heater - Ph t ngoi ghi trờn mỏy Cary IE UV- Visible Spectrophotometer... 126c (ti liu 124-126c [14]) 15 tan: Tan d trong aceton, cloroớorm, tan nhiu trong ethanol núng, ớt tan trong ethanol lnh, tan nhiu trong nc núng v hu nh khụng tan trong nc lnh 2.2.3 Tng hp 5-(m-nitro benzyliden)- thiazoIidin-2,4-dion (II) Chỳng tụi ó tin hnh tng hp cht (II) theo quy trỡnh tng hp ca ti liu [16] *Phng trỡnh phn ng: ^ - N - H A cO II, A cO N a C i 0H 6O 4N 2S; M = 2 5 0 *Tin hnh:... núng chy: 211,5- 213c tan: Khú tan trong nc, MeOH, EtOH, cloroớbrm nhit phũng, d tan hn trong MeOH, EtOH, cloroớbrm núng, tan trong aceton, DMF 2.2.4 Tng hp mt sụ dn cht base Mannich ca 5-(m-nitro benzyliden)thiazolidin-2,4-dion Da vo tớnh cht ca nguyờn t H linh ng trong nhúm -NH kp gia 2 nhúm carbonyl ca nhõn thiazolidin -2,4- dion trong phõn t cht (II), chỳng tụi ó tin hnh tng hp mt s dn cht base... 1,5% pH= 7,0 0,2 Mụi trng Sabouraud lng: Glucosa 2% Pepton 1% pH= 6,0 0,2 29 Mụi trng Saborau c: Glucosa 2% Pepton 1% Th ach 1,5% pH= 6 ,0 0 ,2 2.4.4 Tin hnh Trc khi tin hnh th ta phi ch nh dch vi sinh vt bng cỏch dựng chng ch th mi phỏt trin trờn thch nghiờng sau 24h, cy truyn vo mt ng nghim khỏc cú cha mụi trng canh thang (i vi vi khun) v mụi trng Sabouraud lng (i vi vi nm) Cỏc ng ny c 32-35C ... tớnh sinh hc nh nhúm celon-a,p ethylenic, nhúm amino methyl 2- Th sng lc tỏc dng sinh hc (khỏng khun, khỏng nm) vi hy vng tỡm c cỏc cht cú hot tớnh sinh hc cao, hng ti nghiờn cu sõu hn v sinh. .. *Thiazolidin-2,4-dion (I) *5-(m- nitro benzyliden)- thiazolidin-2,4-dion (II) *3-(anilino mcthyl)-5-(m-nitro benzyliden)- thiazolidin-2,4-dion (III) *3-(p-lỡuoro anilino methyl)-5-(m-nitro benzyliden)- thia/lidin-2,4-dion... methyl)-5-(m-nitro benzyliden)- thiazolidin-2,4-dion (V) *3-(o-cloro anilino methyl)-5-(m-nitro benzyliden)- thiazolidin-2,4-dion (VI) *3-(p-bromo anilino methyl)-5-(m-nitro benzyliden)- thiazolidin-2,4-dion