The complexes were tested fo r biological activities and found to be capable of inhibiting the growth o f som e human cancer cells.. On the basis of the synthesis of potassium tri chlor
Trang 1S/NU JOURNAL OF SCIENCE, Nat Sci & Tech., t.XVIII, n ° l - 2002
SYNTHESIS A N D BIOLOGICAL ACTIVITIES OF SOME
M IXED - CIS DIAM INE COMPLEXES OF PT(II)
CONTAINING PIPER IDIN E A ND OTHER AMINES
D u o n g B a V u
Teacher's Training College o f Kiengiang
T r a n T h i D a , N g u y e n H u u D in h
Facility o f Chemistry, Hanoi University o f Pedagogy
A b s tr a c t Five complexes o f CIS - dichloro (piperidine) (am ine) platinum (II) in cluding [Pt (Pip) (M orpholinejC hi-H 'iO , [P t(Pip)(Pyridine)C k], ỊP t(P ip) ( QuinolineJCIv], IPt.(Pip)(p-PheneUdine)Cl 2 ], [P t(Pip) fa - NaphthylamineJChJJ (Pip = piperidine) have been synthesised and characterized by elemental analysis, molar conductivity, IR and Ra man spectral studies The complexes were tested fo r biological activities and found to be
capable of inhibiting the growth o f som e human cancer cells.
In tro d u ctio n
Many diam ine complexes of P t(II) exhibits high anti-tum or activity Some of which have been used for treatm en t of cancer [1] On the basis of the synthesis of potassium tri chloro piperidine p latin ate (II), K[PtPipCl;j], (P0), [2], the P t(II) complexes containing piperidine and arom atic am ine or heterocyclic amine (Am) have been synthesised The structures of complexes have been determined The complexes were tested for biological activities
R e s u lt a n d D is c u s s io n
Five complexes were prepared according to the Peyrone rule: when a chlorine atom
in the PC) is su b stitu ted by an am ine molecule, the product of C I S - configuration would
be expected The amines used for synthesis included: morpholine, quinoline, pyridine, p
- phenetidine and a - naphthylam ine The synthesis of P t(II) complexes of mixed cis -
diamine were carried out in acidic medium:
Or in aqueous solution of free amine:
All the above-prepared complexes are in yellow acicular crystals They show a sharp trace on TLC The analyses (therm al analysis, spectral analysis ) found out the presence
of crystalline - w ater in P I complex (Table 1) The results of elemental analysis are in a
59
T y p e se t by ^Ị ạ ^S-T^X
Trang 260 D u o n g B a Vu, Tran T hi D a, N g u y e n H u u D inh
good agreement with predicted structures The ưiolar conductivity (fi) of the complexes
in 5.10-5 M solution are in the range 10 -r 14 i i _1cm2 mole” 1 indicates their non - electrolytic nature (Table 1)
T a b le 1: Yield, Rf, Molecular conductivity (/i), Elem ental and
crystalline - w ater composition of the complexes
found
C o m p o s itio n ( %) :
calcd.
The main absorption bands in the IR and Ram an spectra of the complexes are listec
in the table 2 The results show th a t most of the bands characterizing of the same atomic groups are exhibited in bo th spectra
T ab le2 : Main absorption bands in the IR and Ram an spectra of the complexes
Comp.
IR (cm ')/R A M A N (R am ) ( c m 1)
V nii
Veil (aro.) (sa t.)Veil
vCat.
(aro.) (sat.)Sell
v«*
^ P t C l 2 \
P0
PI
P2
P3
P4
(
IR 3 1 7 8 ,3 1 5 5 3061 29 2 4 , 2864 1612, 1601 1450 1 2 0 1 ,1 0 4 3 551
-Ram 3 1 8 2 ,3 1 5 4 3071 2 9 3 4 ,2 8 6 2 1616, 1602 1446 1202, 1024 579
P5
IR 3 2 1 1 ,3 1 8 2 3076 2 9 5 4 ,2 8 5 8 1610, 1512 1456 1155, 1014 442
There is one or two absorption bands for Z'NH at 3200 -3154 cm - 1 , in which one banc characterizes the stretching vibration of NH group of piperidine and morpholine, othei band characterizes the stretching vibration of NH'2 group from arom atic amines in P4 P5 Weak bands a t 3077 - 3055 cm -1 characterize the stretching vibration of CH(aromatic
group There are several bands exhibiting the stretching vibration o f CH(satlưated) grouỊ
a t 2966 - 2850 cm - 1 Deformation vibrations of NH2 group (in P4, P 5) are mixed wit!
Trang 3S y n th e s is a n d biological a c tiv itie s o f so m e m ixe d - CIS d ia m in e 61
the stretching vibration of C = C (aromatic) group exhibited by bands a t 1626 - 1512 c m " 1 Deformation vibrations of C H (Satnrated) are exhibited at 1458 - 1423 cm - 1 In the Ram an spectra, the skeletal vibration V C - C of saturated the ring result in strong bands at 1228 -
1014 c m '1 T he stretching vibration of P t - N bond is observed in the 580 - 440 cm -1 region, th a t indicated the coordination of amine to P t(II) A strong band a t 334 - 318
cm -1 arises from the stretching vibration of Pt - Cl bond The medium bands at 255
- 208 cm "'1 and at 187 - 155cm-1 can be assigned to stretching vibration of N PtC l and deform ation vibration of P tC l‘2 group [3],[4] Besides, bands at 3479 - 3429 cm -1 in the both spectra characterize the stretching vibration of OH group from crystalline water molecule in P i
Thus, the spectra of studied complexes are in good agreem ent with the structural formulas suggested in Fig 1
H-.0
= v
\ /
Pt
/ \
Cl
Cl
c 2 h 5 o
, - - H
Pt
“V / V
P4
Fig 1: The stru c tu ra l formulas of the complexes: P I , P2, P3, P4, P5
T he test for cell cytotoxicity was carried out on hum an liver cancer cell (Hep -
G2) and human heart m em brance cancer cell (RD) IC50 (/ig/m l) values for the tested complexes are given in th e table 3 IC50 < 5 (with pure sample) and IC50 < 20 (with crude sample) are considered to be positive (+ ) The results show th a t P I, P2, P4, P5 are capable of inhibiting the two above cell lines (Hep - G2 and RD); P3 is capable of inhibiting only cell line (RD)
T a b le 3: IC50 (m g /m l) values for Hep - G2 and RD of the tested com plexes
Comp PI* * ( c ru d e samDle) P2 P3 P4 P5 Hep - Gt 8.9, (+) 3.2, (+) > 5.0 (-) 3.9, (+) 3.6, (+)
RD 9.0, (+) 2.8, (+) 2 0 ( + ) 2.9, (+) 3.1, (+)
Trang 462 D u o n g B a Vu, T ran T h i D a , N g u y e n H u u D in h
E x p erim en ta l
1 S y n th e s is
- Synthesis of P I: to an aqueous solution of 2m.mole of morpholine, a solution of
1.111.mole of PO satu rated in w ater was added The reaction m ixture was tirred at 25 - 3 0 °c for 3 hours A yellow precipitate was filtered, washed with cold water and recrvstallized
from ethanol - water m ixture.
- Synthesis of P2: similar to th a t of P I
- Synthesis of P3: to a solution of 3.m.mole of quinoline in acidic medium (pH = 6),
a solution of lm m ole PO sa tu ta te d in w ater was added The resulting solution was tirred and added dropwise w ith 2N KOH solution After about 3.5 hours, a yellow pricipitate was filtered, washed w ith dilute HC1, cold water and recrystallized from ethanol - water mixture
- Syntheses of P4, P5: similar to th a t of P3
2 A p p a ra tu s a n d m eth o d s
- TLC chrom atogram s were obtained on silufol u v - 254 plates (desorption system:
acetone/ nitric acid = 10/1), developed by iodine vapors
- The IR spectra a t 4000 - 400 cm -1 were recorded in K Br discs on a FTIR - 8700 SNO - SHIMADZU spectrophotom eter The R am an spectra were recorded on a Micro Raman LABRAM at 4000 - 100 cm -1 - , using excited radiation a t 632,8 nm from heli - neon laser
- The c , H, N, Cl contents were determined a t HCM city Experim ent center, using
an autom atic elemental analyzer The P t content carried out by weight m ethod at faculty
of Chemistry, Hanoi University of Pedagog The thermal analysis was recorded on a DSD
- 50 instrum ent and TG A - 50 H instrum ent (SHIMADZU) T he molar conductance values
of complex solutions were measured OI1 a conductivity m eter HI - 88119 N
- The cytotoxicity tow ards cancer cells was tested a t th e Experim ental biological Lab., Institute of C hem istry of natu ral compounds, based on th e m ethod being carried out at Nation Cancer In stitu te of America (NCI)
C on clu sion s
Five P t(II) mixed CIS - diamine complexes of P t(II) containing piperidine and other amines have been synthesized including CIS - Dicholoro (M orpholine) (Piperidine) P la t inum (II), CIS - Dichloro (Piperidine) (Pyridine) P latinum (II), CIS - Dichloro (Piperidine) (Quinoline) Platinum (II), CIS - Dichloro (p -Phenetidine) (Piperidine) Platinum (II), CIS
- Dichloro (a- N aphthylam ine) (Piperidine ) Platinum (II)
The structures of the complexes have been determ ined on the basis of elemen tal analysis, therm al analysis, molar conductivity m easurem ent, IR and Ram an spectral studies
The result of testing for cell cytotoxicity shows th a t P I , P2, P4, P5 are capable of inhibiting two hum an cancer cell lines (Hep - G2 and RD); P3 inhibits only cell line (RD)
Trang 5S y n th e s is a n d biological a c tiv itie s o f so m e m ix e d - CIS d ia m in e 63
R e r r e r e n c e s
1 A H F S Drug Inform ation 1990 p.482 - 490.
2 Duong B a Vu Le Hai Dang, Nguyen Nam Trung, T ran Thi Da Interaction of
K-jfPtCLi] w ith piperidine or morpholine Journal o f Sciences (in Vietnamese)
Hanoi University of Pedagog, No 4(2001)
3 Nguyen H uu Dinh, Tran T hi Da Application of some spectroscopic methods in study
on the structure o f molecules Education Publishing House, Hanoi (in Vietnamese) (1999)
4 K Nakamoto Infrared spectra in Inorganic and coordination compounds Wiley,
New York (1970)
T A P C H Í K H O A H Ọ C Đ H Q G H N , K H T N & C N , t X V III n ° l - 2 0 0 2
TỔNG HỢP VÀ HOẠT TÍNH SINH HỌC CỦA MỘT s ố PHỨC CIS - DIAMIN
HON TẠP CỦA Pt(II) CHỨA PIPERIDIN VÀ CÁC AMIN K.HÁC
Dương Bá Vũ
Trường Cao Đẳnq Sư phạm Kiên Gianq
Trần Thi Đà, Nguyễn Hữu Đĩnh
K hoa Hoá, Trường Đ ại học Sư phạm H à Nội
Năm phức cis - diamin hỗn tạp của platin (II) chứa piperidin và amin khác
[Pt(Pip)(p-Phenetidine)Cl'2], [Pt(Pip) (a- Naphthylamine)Cl2)] với (Pip = piperidine) đã được tổng hợp và nghiên cứu cấu trúc bởi phương pháp phân tích nguyên tố, đo độ dẫn
điện phân tử, phổ IR và Raman
Kết quả thứ nghiệm cho thấy các phức thu được có khả năng ức chế sự phát triển
của một số dòng tế bào ung thư người.