T O N G HQfP, N G H I E N ClTU CAU T R l f C V A T H A M D O H O A T TTNH SINH H O C CUA FHlTC C H A T C o ( n ) VOfI 4 - M E T Y L T H I O S E M I C A C B A Z O N S A L I X Y L A N D E H I T
DAO THI THUY HANG Trudng Cao ddng Cdng nghiep Tuy Hda
DUONG TUAN QUANG Trudng Dgi hgc Su phgm - Dgi hpc Hue
Tdm t i t : Phiic chit cua Co(n) vdi 4-metyltMosemicacbazon salixylandehit da duge tdng hop. Dd li nhOng tinh thg mau xanh rgu, tan tdt tiong Dimetylsunfoxit va Dimetylfomamit. Hgp chit nay d i dugc die trung bdi cac phuang phap phd MS, NMR ciing nhu do do din di?n. Ket qua cho thiy phuc chat cd ti le kim logi/phdi tu = Yi.
Hogt tinh sinh hpc cua phdi tir va phiic chat cOng da dugc khio sit.
Nhin chung, hogt tinh d phiic chit cao ban d phdi tu.
I.GICJITHISU
Thiosemicacbazon v i phiic chat ciia chiing da dugc nghien cuu rdng rai hon 30 nam qua do cd hogt tinh sinh hpc dgc biet [1], [2], [3], [4]. Cac nha khoa hpc da cM ra rang he thdng 3 cing NNS cd mgt d thiosemicacbazon thi hien hoat tinh tic chi sy phit tngn cua nhilu Ioai khdi u [1], [2], [3] va phiic chit thudng cd hogt tinh cao hon phdi tu ty do [5], [6], [7]. Cac nghign cuu cung cho thay hoat tinh eiia phiic chat vdi thiosemicacbazon ttong te bio sdng cd hen quan den sy lien hgp ciia phdi tir v i cau titie ciia phdi tti [8]. Mac dii d i cd nhilu cdng tiinh ngMen ciiu vg phuc chit cua hgphdi tii nay nhung vin chua tiiiy kit qui ngMen cuu ve phiic chit ciia din suit 4- metyltiiiosemicacbazon salixylandeMt vdi cac kim loai chuyin tiep, die biet vdi Co(II).
0 bai bao niy chung tdi trinh biy ket qua ngMen curu phirc chit tgo thanh giiia Co(n) vdi 4-metyIthiosenncacbazon salbcylandehit, tip tnmg vio viec khai thic ciu true dua tten mdt sd phuang phap hign dgi. Chiing tdi cung ttinh biy nhung kit qui so bd vl thu nghigm hogt tinh khang vi sinh vat kilm dinh va khi nang uc che su phat tiign tl bao ung thu gan (Hep-G:), ung tiiu phdi (Lu) va ung thu co van tim (RD).
2. THUC NGHIEM 2.1 Miy mdc va thilt bi
Phd khdi lugng dugc do tten may LC-MSD-Trap-SL (Nhit), Vien Hoi hpc, Vien Khoa hgc va Cdng ngh? Vigt Nam.
Phd cdng hudng tir proton dugc do tien may cgng hudng tii hat nhin phan giii cao 500 MHz (Brucker Due) d nMet dp phdng tgi phdng cdng hudng tir hat nhin, Vien Hoi hpc, Vi?n Khoa hoc vi Cdng nghe Viet Nam.
Tap chi Khoa hgc va Giao due, Truong Dai hoc Sir pham HuS ISSN I859-I6I2,S6 04(20)/201I:lr. 13-18
DAO THI THU-Y HANG - DUONG TUAN QUANG
Dp din dien dung dich dugc do tien may EC300, Vien Hoi hgc, Vien Khoa hgc va Cdng nghe Viet Nam.
Hoat tmh sinh hgc cua phiic dugc dgc tien miy ELISA d budc sdng 495-515mn tai Phdng Sinh hgc Thuc ngMem, Vien Hoa hpc cic hgp chit tMen nhign, Vien Khoa hpc va Cdng nghe Viet Nam.
2.2. Tdng hgp phih: chat
Phiic chit dugc tdng hgp nhu sau. Hda tan Co(N03)2-6H20 vdi lugng du 10%
(0,1665g) vao 10ml nude cit (dd A). Hda tan 0,2090g phdi tu 4-metylthiosemicacbazon salixylandehit (H24methsa) vao 20ml ancol etylic tinh kMet (dd B). Trpn hai dung djch nay lai vdi nhau v i dieu chinh tdi pH=7 bang natriaxetat. Hdn hgp phin ung dugc dun hdi luu khoing 2h d SO^C. Tir dung dich se tach ra nhirng tinh the min mau xanh rgu.
De ling idioing 1 gid, lgc thu tinh the va rira nhigu lan bing hdn hgp C2H5OH/H2O rdi kgt tinh lgi tir hdn hgp DMF-H2O- Sau do lam khd ttong binh hut i m chiia silicagel.
3. KET QUA VA T H A O LUAN 3.1. Phd khoi lugng (MS)
Hinh 1. Pho khdi lugng cua phuc chat
Trong phd khdi lugng cua phiic chit chura cym pie vdi m/z = 475, 476, 477 duge gin eho cum ion phan hi ciia hgp chit cd thanh phin [Co(H4methsa)2]. Ti 1? pic M, M+1, M+2 phii hgp vdi cac gii ttj tinh toan li thuylt.
Phd khdi lugng xuit Men pic m/z = 460, 461, 462 ung vdi ion [Ci7Hi702N6S2Co]*do mit dl mgt nhdm -CH3 tir ion phan tii v i xuit hign pic m/z = 445,446,447 ung vdi ion [C17H16O2N5S2C0]* do mit di mgt nhdm -NH-CH3 tir ion phan tii. Minh vd ciia phiic chit [C17H16O2N5S2C0]* mit di mdt nhdm -CH3 v i ion tao tiianh kit hgp tiiem mgt nguygn ni H lam xuit Men pic m/z = 431 ung vdi cdng thirc [Ci6H|402N5S2Co]''. Minh vd ciia phiic chit [Ci7H,602N5S2Co]'' mit di mdt nhdm -NH-CHs v i ion tao thinh kit
TONG HOP, NGHIEN COU CAU TKUC VA TRAM DO HOAT TiN"H SINH HOC...
hgp thgm mdt nguyen tu H lam xuat Men pic m/z = 416 ung vdi cdng thiic [C,6H,302N4S2C0]^
Su pha vd mdt phin phirc din dgn sy xuit Men eiia pic m/z = 209 ling vdi ion [C9HiiON3S]"(ion phdi tii). Ngoii ra tiong phd cdn xuit Men cac manh [CgHgONsS]", [C7H6ON]-...
3.2. Pho cgng humig tir hat nhSn
So sinh phd thyc ngMem ciia phiic ma chiing tdi nhin dugc vdi phd md phdng, chiing tdi quy kgt cac tm Meu xuit Men trgn phd thyc ngMem cua phiic nhu sau:
TP
'tf'
81 2.47H5C—N—C—N—N=CHs
1 I 1 1 Hi 1
IMr 7.22'
1 9.83 1 OH
^ ^ 6 . 9 3 7 J 2
1 in B
.
Hinh 2. Phd 'H-NMR mo phdng ciia H:4methsa
3L JLf u_
ll
Hinh 3. Phd 'H-NMR cua phuc chdi
Nhm chung dp chuyen dich hda hgc cua cae proton tiong vdng tham thay ddi khdng dang ke so vdi phdi tir, 6 = 7,586 - 7,017ppm (4H).
DAO THI THUY HANG - DUONG TU.^N QUANG
Dilu dang chii y la tin Meu 61 l,67ppm tuang ung vdi proton cua nhdm NH-hidrazin d phdi tir khdng cdn thiy tien phd ' H - N M R eua phirc chat. Do do cd till kit luin ring kM tao phiic phdi tOr da chuyin tir dang tiiion sang dang tMcI.
-c—N—N=CH
Tin higu singlet xuit Men d vimg trudng ylu nhit cd dp chuyen dich hda hgc 610,419 ppm tuang ling vdi proton ciia nhdm OH, do chuygn dich cao han so vdi phdi tii. Digu do cd thi giai tMch nhu sau, khi tao phuc cic election se chuyen djch ve pMa ion kim logi va lam giam tie dung che chan proton gin do, tin Meu edng hudng se djch vg pMa trudng thip han.
Tin hieu 68,327ppm tirang ling vdi proton cua nhdm CH. Tin Meu 52,577ppm cd cudng dp tich phin - 3 ung vdi proton ciia nhdm CH3 ttong phiic chit. Tin Men 61,952ppm tuang ling vdi proton nhdm NH-amit.
Cic tin hieu phan giai khi tdt tten phd cho thay day la phd 'H-NMR ciia phiic [Co(H4methsa)2] tinh khiet vi ngu la hdn hgp hai phuc phd gM dugc se cho nhimg tin higu khdng rd rang. Dieu niy ciing da dugc khing dinh qua viec phan tich phd khdi tten hinhl.
Tdng hgp cac ket qui tir phd khdi lugng v i phd cgng hudng tir hat nhin chiing tdi dg nghi ciu tnic ciia phuc chit dudi day. Ciu tnic nay phu hgp vdi dp din dien eiia dung dich li: //=28,4 ohm"'.cm'.mol"'
3.3. Ket qua thir hoat tinh sinh hgc
a) Ket qua thu hoat tinh khans vi smh vat kilm dinh STT
1 2
Hop chSt H24methsa [Co(H4methsa),1
Nong dg i^c che toi thieu MIC {jig/ral) Vi khuan Gr(-)
E 50 12,5
P 25 25
Vi khuan Gi(+) B 50 25
S 50 25
Nam SOI A 25
F 25
.
Nam men S"
50 50
C 50
.
TONG HOP, NGHIEN CUU CAU TRUC VA THAM DO HOAT TFNH SINH HQC,..
Ket qua tign cho thiy ca phdi tii va phiic cliat Co ciia ehiing dgu cd kha ning khing nim, khing khuin. Tuy nhien hoat tinh ciia phuc chit manh hon so vdi phdi tii. Die biet, phiic tdng hgp eho boat tinh mgnh ddi vdi khuin E. Coli, diy la loai khuin gay nguy hai rit Idn ddi vdi sire khde con ngudi.
b) Kgt qui thu hogt tinh khing ung tiiu STT
1 2
Hgp chat H74methsa rCo(H4methsa),l
Dong le bao (IC50, tig/ml) Hep-G2
4,89
>5 Lu
>5
>5 RD
>5 1.39 Hep-G2' ung thu gan; Lu: ung thu phoi; RD: ung thu co van tim
Nhin chung, phdi tii khdng cd khi nang tic che sy phit tiien cua 3 ddng tl bio ung thu khio sat. KM tao phuc kha ning tie chg su phat trien ciia te bao RD ting len ding ke.
Dieu nay dugc thi hien qua gii tri IC50 tuong ddi thip.
4. KET LUAN
Da tdng hgp dugc phiic cua 4-metylthiosemicacbazon salixylandehit vdi Co(II). Bing phuong phap phd MS, da xac dinh duge thanh phan v i cau tnic ciia phiic. Su dung phd NMR, do dd dan dien dg khing dinh Igi ciu tnic phiic. Phiic thu duge cd hogt tinh sinh hgc manh.
TAI LlfU THAM KHAO
[1] S. Padhye, G. B. Kauffinan (1985). Transition metal complexes of semicarbazones and thiosemicarbazones. Coord. Chem. Rev., Vol. 63, P. 127-160.
[2] P. N. Y. Kotsis, D.K. Demertzi (2001). Platinum(II) and palladium(II) complexes with 2-acetylpyridine thiosemicarbazone: cytogenetic and antineoplastic effects.
Anticancer Drugs, Vol. 12, P. 65-74.
[3] D. Sriram, P. Yogeeswari, P. Dhakla, P. Senthilkumar and D. Banerjee (2007). N- Hydroxythiosemicarbazones: Synthesis and in vitto antitubercular activity.
Bioorganic & Medicinal Chemistry Letters 17,P. 1888-1891
[4] R. A. Gupta, A. K. Gupta, L. K. Soni and S. G. Kaskhedikar (2007). Rationalization of physicochemical characters of oxazolyl thiosemicarbazone analogs towards raulti- dmg resistant tuberculosis: A QSAR approach. European Journal of Medicinal C/iemisrrv, Vol. 42, No 8, P. 1109-1116.
[5] D. K. Demertzi, P. N. Yadav, J. W., S. Skoulika, T. Varadinova and M. A. Demertzis (2006). Zinc(II) complexes derived fiom pyridine-2-carbaldehyde thiosemicarbazone and (lE)-l-pyridm-2-ylethan-l-one thiosemicarbazone. Synthesis, crystal structures and antiprohferative activity of zmc(II) complexes. Journal of Inorganic Biochemistry, Vol. 100, No. 9, P. 1558-1567.
[6] K. Husain, M. Abid and A. Azam (2007). Synthesis, characterization and antiamoebic activity of new indole-3-carboxaldehyde thiosemicarbazones and their Pd(II) complexes. European Journal of Medicinal Chemistry, Vol. 42, No. 10, P.1300-1308.
DAO THI THUY HANG - DUONG TUAN QUANG
[7] N. T. P. Chi, N. H Nam, D. T. Quang (2004). Nghien cuu tdng hgp, hoat tinh sinh hpc ciia mpt so phirc chit cua kim loai chuyen tiep vdi thiosemicacbazon. Tgp chi Y hpc thuc hdnh, Sb 10, tt. 11-13.
[8] D. X. West, H. Gebremedhin, R. J. Butcher, i. P. Jasinski, A. E. Liberta (1993).
Structures of nickel(II) and copper(II) complexes of 2-acetylpyridme azacyclo- thiosemicaibazones. Polyhedron, Vol. 12, No. 20, P. 2489-2497.
Title: SYNTHESIS, STRUCTURE ELUCIDATION AND BIOACTIVITIES OF Co(II) COMPLEX OF SALICYALDEHYDE 4-METHYLTHIOSEMICACBAZONE
Abstract: Co(II) complex of salicylaldehyde 4-methylthiosemicacbazon has been synthesized and characterized by MS, NMR spectrometties as well as electrical conductivity measurement.
The complex was a moss green crystalline compound, soluble in Dunethylsunfoxite and Dimetylfomamite. It was found that the complex had a metakligand stoichiometiy of 1:2. The biological activity of 4-metylthiosemicacbazon and the complex against the bacteria, fimgi and the ability to inhibit the growth of cancer cells were also tested.
ThS. DAO THI THUY H A N G Trucmg Cao ding Cdng nghiep Tuy Hoa PGS. TS. DUONG TUAN QUANG
Khoa Hda hpc, Tnrtmg Dai hpc Su pham - Dai hpc Hue
