BO GIAO DUG VA DAO TAO TRU'O'NG OAI HOC TONG HOP HA NOI PGS PTS PHAM TRUONG THI THO NGHIEN CLTU BAN TONG HCfP DjNH HU-QNG CAC D A N XUAT EUGENOL CO TAC DUNG KHANG NAM C ALBICANS LUAN AN TIEN St KHOA HOC HOA HOC HA NOI 1994 MUC LUC Phan mot Trang Chirang ma dau - Gidi thieu luan an - Muc dich nghien cau cua luan an - Tom tat cac luan diem co ban ciia luan an va nhung ^ dong gop mdi cua tac gia Cinrang tong quan 0-1 Cac dan xuiit eugenol dupe biet den 0-2 Van de nam benh; NhOng nhom khang sinh chinh; NhOng ch^t C tac dung khang nim C albicans O 0-3 V^n de tong hop noi chung va tong hdp cd dinh hudng 12 0-4 Mdi hen quan dinh luong "Cau true hoa hoc va 14 tac dung sinh hgc" (QSAR) ' 0-5 Nhung md hinh toan hpc nghien cuu vtin de QSAR 16 a- Phuong phap nhan dang, phuong phap phan tich cau true 16 b- Giai phap ve cac Juong til thdng ke 17 c- L/ng dung phan tich nhan td de tim hieu quan he c^u true - tac dung d- 18 Cac phuong phap ban thue nghiem de nghien cuu co che cac phan ung cua cac chat cd tac dung sinh hoc 19 e- Phuong phap hoi qui nhieu thdng sd 20 g- Phan tich cQu true - lac dung theo phuong phap Hansch 23 h- Md hlnh toan cdng tinh Free - Wilson i- Nhung nghien cuu ly thuyet ve mdi lien quan cau true hoa hpc - tac dung sinh hpc 26 29 Chu'wng I: Doi tin/ng nghien cii'u, muc dich cua cong trlnli, va cac piiu'irng plidp ngiiien cii'u 1-1 Ddi tuong nghien cuu 33 1-2 Muc dich cua cdng trinh 34 1-3 Cac phuong phap nghien cuu 34 Phan hai NHUNG KET QUA NGHIEN CUU Cliitrang 2: Mot so ichdo sat ma dau 2-1 38 trang (Ocimum gratissimum L., Labiatae) Viet Nam 2-2 Nghien cuu phan hda hpc tinh dau huong nhu 40 Khao sat dinh tinh tac dung khang khuan, khang nSm 40 cua tinh dau huong nhu va eugenol 2-3 Nghien cuu quy trinh tdi uu tach eugenol tu tinh dau huong nhu 42 2-4 Nhung nghien cuu md dau chuan bi cho viec ban tong hop 45 cac din xuat eugenol 2-5 Nghien cuu su phan bd dien tich cua nguyen tu phan 49 tu eugenol, isoeugenol vave gidn phan tir cua chung theo chuong trinh Alchemy II va phuong phap CNDO/2 Cliwang : Ban tong hap cac dan xuat eugenol tiieo quy lioach, 3-1 Ban tong hop cac dan xuat eugenol theo quy hoach 3-1-1 Lua chpn cac nhdm the'va vi tri thay the phan tu eugenol 52 52 52 3-1-2 Sd luong cac dan xuat can tong hpp theo md hinh Free - Wilson 53 3-2 Ban tong hop cac dan xuat eugenol 55 3-2-1 Nhu*ng phan trng ca ban lam thay doi nhom chuc alyl 3-2-1-1 Dbng phan hoa ^5 3-2-1-2 Hydro hoa 56 3-2-1-3 Oxy hoa ' 3-2-1-4 Halogen hoa 57 58 * Xac dinh cau true VH (1-hydroxy - 2-metoxy 4 E F: F R' 500> ; 16 7 I ? ' 766394 335E -00 5.46 C (2 i 7^21 6yrOE-00,1 73 C o n f i c* £ r 'Z •? c o ' t t i c i e tl t • ^ ? ^ ' 95 ^'^^ - ' I Phuong trinh 99 " r", ^ M ' \.i^ RCi- ' T R B L E 0P 11 E R M ' ij H P E * = x O f r - J 3- I IJ F L E J TOrRL REGP ^ n, 1 \ (u ^ ' R E c I L l F - C R t 11E ?• , 15952 _• J 1.41593 04514 R-3 0C HF E D l ' = ^ 31 36 31^ 5.7 M M 3T0 E' POP UP E T = 21247 P ri^ £ I C O N T ' M h, ( r i e a d - t r " = i • ' o f ^ fine I t REi P E ' 'RR C0H3T t rn t rn I ON COEFFICIEMT3 3TD FORMRT 3TD ERROR I 3571 10994 34333 13694 ' 40 02 072 32 ' 'HP E-FORMHT T-ORLUE i:.0H3T 357103722E+000 25 99 d f r.i 433313253E-00t 51 t rn vj 6 E - 0 60 C 'J n t 1«J e ri c e c ct e f f i c i e r"r t i ,= a Pi q "=; Q -I| i rr '/ • T0 R E3 I DU RL •1 n I I cn •>! '— I — t •-' C't cn — ( — i — I — I — i — I — i — I — I - + j-'^^mv mm^-^ -m m^-^ Phuong trinh 100 •-" OC't^ L E T n l ^^L F' E i : F C ?F R rn PE3i U Of-" MERM P - •'••'RCUE 3uljRPt - i" 9 '6 4949 J ':* 0411 1 19.43 Pi 7! 2 P - '• Ij Ij R F' E = F: 6 4 e y : 3TC1 2PP0R OF EST = 20283 P r- c - • L Ll M T ' •z o r i t r, I I e FP^:F•E '.,.' R F' COtJi r L?P Pr.i 11 h t? r'' res d > t n I LiN COEFF I C lENTS 3TU FOPMRT 3TD ERROR 2,33290 13421 , 3 J 'S Cl _ M P, \^ ' , * 01943 L^P E-FORMRT T-yRLUE 3 413 E + 0 12.66 3450334i7E-001 6.13 Rrr U'.-' fD i.'HF c I j n 'i r C C' r"i t 'd e ri 'Z e - UE:3t* < 'J a I d 5564 0025 03132 24t43 05F 73 : 0 34 y- 33532 13 703 Pr e ' CONT ;r:rd.Res - 27426 494 1 15632 1464 - 23973 ,04348 - • 14707 , 9V3 -.67544 Ul fi e ri r- e a «J y " T D I.n I J P E I n CJ R L I — I — I 223 59 9Ci E- 002 ^ c o •? t + i c i e n T ( e ' n Phuong trinh 101 HOV 3ni.u-CE Of- Ti'iTHi TRBLE MERb' U R R E ' F-^VRLUE :- P P !: • ,- 3i 23 76 11 40 36 13 39315 1.24622 , 03449 Pr., Pt.,2 P E c •' [ , P - - ' ' IJ R F E C = ^ 3 06 •-.TO ERROR OF E S T , = P f" ^ r ' C Cl M ' 13572 r" -^ a d y \'t ^n I t o i - r , r, 1 t\'_\^ RE6F£ VRR CHNS r Piril Pm2 iuM ro T S;-: s • - n ^ o p; ^ ^ F - F O R M R T T-VRLUE ? Ll f '-• '^ E + 0 - * _ 2.34 'j i E - 0 " 2.77 P 4 66 E - 0 ; 6.01 '.R 'R con3r Fn, Rm2 t t 'Z i e rt t n t 'J •? r-i iz •?v'^ >e : l^'T'-J Y Pr-edi : Obz-r• V »? d ''(' "7 13319 ^ 266y^y^ • 5r [ n f1 Cl • ^ 72134 d S F; 50 0, c 33473 49 40 a 1300 07251 "7 44929 - 2900 ' ~7 56273 20 0 • ~7 2300 67031 ~7 9313 42700 • JPS^ F'r COEFF ICIEHTs F O P M R r S T O ERF OR 3.06736 ,07161 - 405 14625 - he r COM TD I \ji I K^ d R L -•: RE — -^ , ^ .|—I—I—+—\ ix I -i- + G i i i 224 Lvj f.n —(—i—)—I—^ yi^ Ph "•ong trinh 102 RO 30URCE TOTRL P: E b F' OF F rii F-WRLUE ,5503 JFTT5 I 24622 013 06 33 73 •1 Fni2 I 9P RES ThEiLE Ml MM 31.-! IJ R R E J I "5 14.2 " IT 14 32 13 34 F'' SQUHREO = ^ ? 35"76 STO ERROR o r E3 :3 ^ P ress ' COM T ' f'ihen i •^ a d y t o iz or'i t riU'T ro EKROP 43054 32629 24723 27303 E-FORMRT 3 i' 6- 61-* £ + 0 699336 I E- 00 14 E - 0 - 4 3 E - 01 L^R C or\ t iJe r i c e c •:• -i- t M c e r i t ' , QS , '^"^ , - 1-URLUE Z 70 STO S ' 'HP cun3 r " Pr.il Pt.,2 L5P _ '••'RR T C0M3T R n-,' F' f,^ 225 pupMM I 31375 57 170 AS 27 2.01 - 53 s > 90 ir.p > •inr atom a torn a t c rn a torn a tern atom atom a torn a torn a torn atom a torn a torn a torn a tom a torn atom a tom atom atom atom atom atom atom MIW MMX Motecuic m - r(infnrni;Ui mmtype charge n mmtype c h a r g e mmtype c h a r g*=^ tl mmtype charge n mmtype c h a r g e n mmtype c h a r g e •1 mmtype 13 c h a r g e n mmt ype c h a r g e mmtype charge a n 10 mmtype charge # 11 mmtype 28 charge ^ 12 mmt ype Z charge tf 13 mmtype charge # 14 mmtype charge 15 mmtype charge n n 16 mmtype charge # 17 mmtype charge 18 mmtype charge n 19 mmtype charge n n 20 mmtype charge n 21 mmtype charge n 22 mmt ype charge n 23 mmtype cha cge n 24 mmtype charge # 0 -0 -0 -0 -0 -0 -0 -0 0 0 0 0 0 without kinc pairs od oxvucn 000 163 38 • 000 038 000 163 127 127 216 216 oxvuen oxygen 33 038 000 038 038 000 000 000 038 038 000 000 000 HMX f:ne rgy • 15 81 36 BND STR 0't 58 S-B 07 TOR VDW 52 D I P / C H R G 23 DipoJ Q Moment OJ ' -43 - 8? kca /mo le ; Heat of Forma t ion 13 361 Strain Energy \-\ ?y ,V^ _ 226 ILH MOL_MM.OUT 3tom atom atom atom atom # # # # T atom rr atom S atom # atom # atom i^ atom * atom # atom ? atom ? ^ atom # atom # atom # atom n atom ^ atom # atom # atom # atom # atom # atom # atom # atom # atom # atom # atom ? atom # atom ;? atom T atom r f atom ^ atom ^ atom ? ^ atom ^ atom ^ nom ^ ^•tom ^ '.torn ^ 7?3'o7r^ cuj.€c: mmtype c h a r g e : mmtype charge: mmtype charge: mmtype charge: mmtype c h a r g e : mmtype c h a r g e : mmtype 13 c h a r g e : mmtype charge: mmtype c h a r g e : 10 mmtype charge; 11 mmtype 18 c h a r g e : 12 mmtype charge: n 13 mmtype charge: 14 mmtype \ charge: 15 mmtype charge: 16 mmtype charge: 17 mmtype charge: 18 mmtype charge: 19 mmtype charge: 20 mmtype charge: 21 mmtype charge: 2 mmtype c h a r g e : 23 mmtype charge: charge: 24 mmtype mmtype charge: mmtype 20 c h a r g e : mmtype charge: 28 mmtype charge: 29 mmtype charge; 30 mmtype 20 c h a r g e : 31 mmtype charge: mmtype charge: charge; 3 mmtype charge: mmtype charge: mmtype mmtype 20 c h a r g e ; mmtype 20 c h a r g e : 38 mmtype charge: charge: m.mtype charge: 40 mmtype 41 mmtype charge; charge: mmtvce ^A- 000 0.163 -0.038 000 -0 038 000 -0.163 n ^ T• 127 133-"'' 792 -0.038 -0.038 0.000 -O' 7 -0.038 0.119 -0.033 -0.038 0.000 -0.038 0.000 ••'zr^.^'>:7z yZ- x"- z:cy^.I9 OJ ron rEHEPAT-H UMPEKTOP: J^- 1/ i MHCTHTYT 3A M305PETEHMB H PAUH0HAAH3AUMH ^ • \ r^fess^ i % > ^ 43771 MHK C 07 C / 2 Ha oc2ioaafcaie ^CT,22 o r 3axoua aa iiaoOperetuiHTa H pamioHaiiK3aLu