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Review Article
BIOLOGICAL ACTIVITIES OF PURINE ANALOGUES: A REVIEW
Sachan Dinesh1*, Gangwar Shikha2, Gangwar Bhavana3, Sharma Nidhi4, Sharma Dileep5
1
Department of Pharmacy, Sri Rawatpura Sarkar Institute of Pharmacy, Datia-475661). M.P., India
Project Directorate for Farming Systems Research (PDFSR) Meerut-250110. U. P., India
3
Central Drug Research Institute, Lucknow-226001.U.P., India
4
Smt. Vidyawati College of Pharmacy, Jhansi- 284121. U.P. India
5
Sri Rawatpura Sarkar Institute of Technology and Science, Datia-475661. M.P.,India
*Email: [email protected]
2
Received on: 12/03/12 Revised on: 13/04/12 Accepted on: 17/04/12
ABSTRACT
The purine analogues are a new class of nonclassical antimicrobial agents that bind with riboswitches. Purine (adenine) analogues are having antimicrobial,
antifungal, antitumour, antiproliferative, antiviral and activity against HSV-1. Riboswitches are structured RNA domains that can bind directly to specific
ligands and regulate gene expression. These RNA elements are located most commonly within the non-coding regions of bacterial mRNAs, because these
genes were involved in fundamental metabolic pathways in certain bacterial pathogens. Purine-binding riboswitches may be targets for the development of
novel antimicrobial agents. In vitro the designed compounds can be bound by purine riboswitches aptamer with affinities comparable to that of the natural
ligand and many of these compounds also inhibit microbial growth.
KEY WORDS: Purine analogues, Introduction, Biological activities.
INTRODUCTION
Purine is a heterocyclic, aromatic, organic compound,
consisting of a pyrimidine ring fused to an imidazole ring.
Purines, including substituted purines and their tautomers, are
the most widely distributed kind of nitrogen-containing
heterocyclic compounds present in nature1.
Heterocyclic compounds are organic compounds (containing
carbon) that have a ring structure containing atoms in
addition to carbon, such as sulfur, oxygen, or nitrogen, as part
of the ring. Aromaticity is a chemical property in which a
conjugated ring of unsaturated bonds, lone pairs, or empty
orbitals exhibit stabilization stronger than would be expected
by the stabilization of conjugation alone. Imidazole refers to
the parent compound C3H4N2, while imidazoles are a class of
heterocycles with similar ring structure but varying
substituent’s.
Purines and pyrimidines make up the two groups of
nitrogenous bases, including the two groups of nucleotide
bases. Two of the four deoxyribonucleotides and two of the
four ribonucleotides, the respective building blocks of DNA
and RNA, are purines2. More broadly, the general term
purine also is used in reference to derived, substituted purines
and their structurally related tautomers (organic compounds
that are inter-convertible by a chemical reaction).
Prominent purines (derivatives) include caffeine, and two of
the bases in nucleic acids are adenine and guanine. In DNA,
adenine and guanine form hydrogen bonds with their
complementary pyrimidines, thymine and cytosine. In RNA,
the complement of adenine is uracil instead of thymine.
Purine is also a component in Adenosine triphosphate (ATP),
which stores and transports chemical energy within cells.
Purine was named by the German chemist Emil Fischer in
1884. He synthesized it in 1898. Fischer showed that the
purines were part of a single chemical family3. The structure
of adenine and guanine, two of the four bases in the DNA
molecule, are given in (figure 1).
NH 2
O
N
N
N
H
N
N
HN
H 2N
N
N
H
Adenine
Guanine
Figure 1: Structures of purine bases
In addition to being biochemically significant as components
of DNA and RNA, purines are also found in a number of
other important biomolecules, such as ATP, GTP, cyclic
AMP, NADH, and coenzyme A.
The quantity of naturally occurring purines produced on earth
is huge. Fifty percent (50%) of the bases in nucleic acids,
adenine and guanine , are purines. In DNA, these bases form
hydrogen bonds with their complementary pyrimidines
thymine and cytosine, respectively. This is called
complementary base pairing. In RNA, the complement of
adenine is uracil (U) instead of thymine1.
Other notable purines are hypoxanthine, xanthine,
theobromine , caffeine , uric acid, and isoguanine (Figure 2).
O
O
N
N
O
N
H
N
P u rin e
O
N
theobrom ine
N
H
N
H
O
N
N
O
N
caffine
N
H
N
H y p o x a n th in e
NH 2
O
N
N
N
HN
X an th i n e
O
HN
N
HN
N
H
N
HN
O
O
N
H
uric acid
N
H
N
HN
O
N
N
H
isoguanine
Figure 2: Some notable purines
The name 'purine' (purum uricum) was coined by the German
chemist Emil Fischer in 1884. He synthesized it for the first
time in 18991. The starting material for the reaction sequence
was uric acid, which had been isolated from kidney stones by
Scheele in 17761. Uric acid was reacted with PCl5 to give
2,6,8-trichloropurine, which was converted with HI and PH4I
to give 2,6 diiodopurine. This latter product was reduced to
purine using zinc-dust (Scheme 1).
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Sachan Dinesh et al: Biological activities of purine analogues
O
O
I
Cl
H
N
HN
O
PCL 5
N
H
N
H
N
N
Cl
HI/ PH 4 I
Cl
N
H
N
N
N
I
N
H
N
uric acid
Zn
N
N
H
N
S
N
purine
Purines are found in high concentration in meat and meat
products, especially internal organs such as liver and kidney.
Plant based diets are generally low in purines1. Examples of
high-purine sources include: sweetbreads, anchovies,
sardines, liver, beef kidneys, brains, meat extracts (e.g., Oxo,
Bovril), herring, mackerel, scallops, game meats, and gravy.
A moderate amount of purine is also contained in beef, pork,
poultry, fish and seafood, asparagus, cauliflower, spinach,
mushrooms, green peas, lentils, dried peas, beans, oatmeal,
wheat bran, wheat germ, and hawthorn. Higher levels of meat
and seafood consumption are associated with an increased
risk of gout, whereas a higher level of consumption of dairy
products is associated with a decreased risk. Moderate intake
of purine-rich vegetables or protein is not associated with an
increased risk of gout.
BIOLOGICAL ACTIVITIES OF PURINE
ANALOGUES:
Anti-leishmanial avtivity: The purine ring system possesses
undisputed biological importance and it is considered to be
one of the most important heterocyclic rings in nature. Antileishmanial activity of purines and its derivatives has been
widely reported. Carmo L et al synthesized new tricyclic
purine derivatives with 6 and 7 members and evaluated all
these compounds for their cytotoxic activity and antileishmanial activity on KB (Human epidermoid carcinoma)
and Vero (African green monkey kidney) cells. They have
synthesized 7,8-dihydro-[1,4]thiazino[3,2,4-hi]purine (1),
8,9-dihydro-7H-[1,4]thiazepino[3,2,4-hi]purine (2), 7,8dihydro-[1,4]thiazepino[3,2,4-hi]purine Hydrofluoride (a),
7,8-dihydro-[1,4] thiazepino[3,2,4-hi]purine Hydrochloride
(b)7,8-dihydro-[1,4]thiazepino[3,2,4-hi]purine Hydrobromide
(c) (figure 3)4.
S
S
N
N
N
N
N
N
.H X
N
1
N
a (X = F )
b (X = C l)
c ( X = B r)
S
N
N
N
N
N
Scheme 1: Synthesis of purine from uric acid
N
2
Figure 3: New tricyclic purine derivatives with 6 and 7
members
Among the tested compounds, only 8,9-dihydro-7H- [1,4]
thiazepino [3,2,4-hi] purine hydrofloride (a) showed an
activity against two species of Leishmania (L. amazonensis
and L. chgasi). Therefore this compound showed
antiproliferative activity against these two species (figure 4)4.
.H X
N
N
a (X = F )
Figure 4: 8,9-dihydro-7H- [1,4] thiazepino [3,2,4-hi]
purine hydrofloride
In a similar study, Berman J. D. et al observed and reported
antileishmanial activity of some purine analogs against
Leishmania donavani In Vivo. The dose of orally
administered 9-deazainosine calculated to suppress 50% of
Leishmania donovani amastigotes in hamster livers was 19
mg/kg (body weight) per day; 96 to 99% of Leishmania
organisms were eliminated from the liver and spleen of
squirrel monkeys by 50 mg/kg per day. Because these
activities were greater than that of the experimental clinical
agent allopurinol and comparable to that of the classical agent
parenteral pentavalent antimony, 9-deazainosine should be
considered for clinical development for visceral leishmaniasis
(figure 5)5.
NH 2
N
OH
H
N
N
N
N
OH
H
N
N
N
Ribose
N
Ribose
FO R M YCI N B
FORM Y CIN A
H 2N
OH
N
N
N
N
Ribose
3-DEAZAGUANOSINE
N
Ribose
3-DEAZAGUANOSINE
OH
N
N
N
N
N
N
H
ALLO PURINO L
Figure 5: Various purine derivatives
Antiviral activity: Virus-infected cells have an increased
demand for purine nucleotides which are needed for viral
RNA or DNA synthesis, and this renders the enzyme,
IMPDH, as a sensitive target for antiviral chemotherapy. Nair
et al synthesized 2-functionalized purine nucleosides and
these compounds were tested as antiviral against vaccinia
virus (in vitro)6.
In line with the above study, it was also known at the time
that many adenosine derivatives are biologically active in
vitro but are inactive in vivo because of deamination by
adenosine deaminase to inactive inosine derivatives. We then
made the assumption that a molecule (such as 9-[[2-hydroxy1 -(hydroxymethyl)ethoxy]methyl]adenine) which has all of
the chemical features of deoxyadenosine, but which lacks a
rigid carbohydrate ring structure, would be a poor substrate
of adenosine deaminase. We further reasoned that if the
above compound were also a poor inhibitor (i.e. had low
binding to the enzyme) of adenosine deaminase, then it might
serve as an excellent antiviral agent. This reasoning was
purely intuitive and was based on the assumption that key
viral enzymes would have a less rigorous structural
requirement in their substrates than would the equivalent
mammalian enzymes. Thus a molecule such as 1 might be
exempt from degradation by adenosine deaminase and other
mammalian enzymes but might be accepted as a substrate by
replicative enzymes in viral systems. Ogilve et al synthesized
purine acyclonucleoside series and evaluated these
JPSI 1 (2), MARCH – APRIL 2012, 29-34
Sachan Dinesh et al: Biological activities of purine analogues
vitro and in human tumorxen ograft models. Hu Lin et al
synthesized
O6-alkylguanine
derivatives
(O6-(26
Cyclohexyl)ethoxylguanine and O -Benzylguanine) and
evaluated this for antifungal activity against some species
of fungi, namely Aspergillus niger and Candida tropicalis
using the disc diffusion method11.
compounds for their pronounced antiviral activity against
HSV-17.
Cl
O
N
HO
N
O
N
NH
N
HO
NH 2
N
N
O
Y
N
OR
Y= H
a
OH
OH
b
N
N
Cl
N
NH 2
N
HO
O
N
N
N
HO
N
N
Y
d
OH
OH
Figure 6: Purine acyclonucleoside
In a similar study, Holy et al synthesized a series of dialkyl
esters of purine N-[2-(phosphonomethoxy) ethyl] derivatives
substituted at position 2, 6, or 8 of the purine base and
evaluated these compounds for antiviral activity8.
NH 2
N
N
Br
N
N
O
P(O)(OR') 2
R = NH 2 , R' = H
O
SH
N
N
N
N
HN
H 2N
N
O
R = C3H 7
R=
Br
N
N
O
P(O)(OR) 2
P(O)(OR) 2
R=H
Figure 7: dialkyl esters of purine N-[2-(phosphono
methoxy) ethyl] derivatives
In a similar study, Yahyazadeh et al synthesized
'carboacyclic' nucleoside analogues such as 1 and purine
derivatives with simple 9-hydroxyalkylsubstituents, such as 2
and 3. These compounds were evaluated as potent antiviral
activities9.
In the same context, Murti et al synthesized N-9 substituted6-chloropurine derivatives and evaluated these compounds
for their antiviral activities against Japanese encephalitis
virus (JEV). None of the synthesized compounds have
significant antiviral activity10.
Antimicrobial Activity:
a- Antifungal Activity: The purine derivatives are of great
importance to chemists as well as to biologists as they are
bfound in a large variety of naturally occurring compounds
and also in clinically useful molecules having diverse
biological activities. Moreover, they are known to possess
antitubercular, antiulcer, antimicrobial, antineoplastic,
antitumor, antiviral and cardiotonic properties. O6Alkylguanine derivatives are considered to be of major
importance for the induction of cancer, mutation, and cell
death. These adducts direct the incorporation of either
thymine or cytosine without blocking DNA replication,
resulting in GC to AT transition mutations, which provide
a mean to effectively inactivate the O6-alkylguanine-DNA
alkyltransferase (AGT) protein and increase the
chemotherapeutic effectiveness of alkylating agents in
ONa
,
Y= NH 2
c
R
N
H
N
ONa
N
O
F
H 2N
Figure 8: O6-alkylguanine derivatives
Purine bases modified in the 6-position and their derivatives
and analogues possess a wide range of biological properties
such as antitubercular, fungicidal, antiallergic, antimicrobial,
antitumor, antihistamic, myocardium inhibiting agent etc. In
the same context, Hu Lin et al synthesized 6-substituted
purines [N6-cyclopropyl-9H-purine-2,6-diamine, N6-phenyl9H-purine-2,6-diamine, N6-[3-(trifluoromethyl)phenyl]-9Hpurine-2,6-diamine,
N6-[4-(2,2,2-trifluoroethoxy)phenyl]9H-purine-2,6-diamine (1-4)], [2-Amino-6-fluoropurine, 2Fluoro-6-fluoropurine, 2-Hydroxyl-6-fluoropurine, 2-Amino6-trifluoromethylpurine, 2-Fluoro-6-trifluoromethylpurine, 2Hydroxyl-6-trifluoromethylpurine,
2-Amino-6trifluoroethylpurine,
2-Fluoro-6-trifluoroethylpurine,
2Hydroxyl-6-trifluoroethylpurine (5-13)] and evaluated for
their antifungal activities against some species of fungi,
namely Aspergillus niger, and Candida tropicalis using the
disc diffusion method, and most of the compounds showed
promising activities12.
NHR 1
H 2N
F 3C
N
N
N
N
H
,
R1 =
,
,
F3CH 2CO
1-4
F
R2
N
5-13
N
H
OCH 2CF 3
CF 3
N
N
N
N
R2
N
N
H
N
N
R2
N
R 2 = NH 2, F, OH
N
H
Figure 9: 6-substituted purine derivatives
In a similar study, Murti et al synthesized N-9 substituted-6chloropurine derivatives and evaluated these compounds for
their antifungal activity against Aspergillus niger and
Candida albicans, and none of the synthesized compounds
have significant antifungal activity10.
Antibacterial Activity: Novel purine derivatives are a
privileged structure present in many biological active
compounds. The previous research on purine derivatives
showed that purine derivatives exerted pronounced activities
like antimicrobial, antimycobacterial, anti autoimmune,
cytostatic and antiviral activities. In addition some 6chloropurines constitute an important class of compounds
possessing diverse type of biological properties including
cytotoxic and antiviral. Keeping in view the diverse
therapeutic activities of 6-chloropurine derivatives, Murti et
al synthesized N-9 substituted-6-chloropurine derivatives and
evaluated these compounds for their antibacterial activity
against Escherichia coli, Pseudomonas aeruginosa,
Staphylococcus aureus, Bacillus subtilis, and reported that
JPSI 1 (2), MARCH – APRIL 2012, 29-34
Sachan Dinesh et al: Biological activities of purine analogues
none of the synthesized compounds have significant
antibacterial activity10.
In line with above study, Gordaliza M. et al isolated
agelasines, asmarines and related compounds as natural
products having a hybrid terpene-purine structure from
numerous genera of sponges (Agela sp., Raspailia sp.) and
some of these natural products have exhibited broadspectrum antibacterial activity against a variety of species,
including Mycobacterium tuberculosis13.
Phosphodiesterase inhibitor: Phosphodiesterases (PDEs)
are enzymes which catalyze the hydrolysis of 3’, 5’-cyclic
nucleotides cAMP and cGMP to their 5’-monophosphates.
PDEs are classified into seven families, five of which,
PDE1—PDE5, are characterized. 1) For instance, PDE4
specifically hydrolyzes cAMP and exerts antiinflammatory
and tracheal relaxant activity. Recently, it was reported 9benzyladenines as potent and selective PDE inhibitors, in
which 9-(2-fluorobenzyl)-N6-methyladenine (BWA 78U)3)
and its 2-trifluoromethyl congener (NCS 613)2) were found to
be selective inhibitors of PDE4. However, purines bearing
halogen at nucleobase have not been examined for their
inhibition of PDEs in the literature. Because biological
activities
of
6-chloropurine
and
2-chloropurine
nucleosides4,5) have been reported, we are interested in the
activity of purine analogs bearing chlorine at the base moiety.
2,6-Difluorobenzyl group was introduced in the
anticonvulsant agent (534U87),6) so this group was chosen as
a substituent at N9 of purine. In this paper, synthesis of 9(2,6-difluorobenzyl)-9H-purine analogs bearing chlorine at
the base moiety and their inhibition of PDEs are described.
Kozai et al synthesized 9-(2,6difluorobenzyl)- 9H-purines
(2,6-dichloro-9-(2,6-difluorobenzyl)-9H-purine,
2,6Dichloro-7-(2,6-difluorobenzyl)-7H-purine, 2,6-dichloro-9(2,6-difluorobenzyl)-9H-purine,
2,6-Dichloro-7-(2,6difluorobenzyl)-7H-purine,
2-chloro-9-(2,6difluorobenzyl)adenine,
6-Chloro-9-(2,6-difluorobenzyl)9Hpurine) and evaluated these compounds as inhibitors of
phosphodiesterase (PDE, PDE1 to PDE5) isozymes14.
Cl
X
X
N
N
N
N
F
X = Cl
X = NH2
X=H
N
N
F
NH 2
N
N
Cl
Cl
R6
N
7
9
N
N
N
R 6 = C l,
N
BnO
OBn
Figure 11: Purine derivatives of L-Ascorbic acid
The naturally occurring N-(purin-6-yl)amino acids are
important intermediates in biochemical processes.
Adenylsuccinic acid (9-ribosyl-6-aspartopurine-5'-monophosphate) is an intermediate product in the amination of inosinic
acid (IMP) to adenylic acid (AMP). Also, synthetic 6- and 9substituted purine derivatives have been previously reported
for their antitumour and antiviral activity, as cardiovascular
agents and for their use as hepadnaviride-active antiviral
agents. Therefore in line with above study, Shalaby et al
synthesized new N-(purin-6-yl)-amino acid and -peptide
derivatives expected to have antitumour activity. All these
compounds were evaluated for Anti-tumour activity against
60 human tumour cell lines derived from nine cancer types
(leukaemia, non-small cell lung, colon cancer, CNS cancer,
melanoma, ovarian cancer, renal cancer, prostate cancer and
breast cancer) according to a well known procedure16.
R
NH
N
N
Ar
C
H
N
F
Figure 10: 9-(2,6difluorobenzyl)- 9H-purines
Antitumour Activity: L-Ascorbic acid and its derivatives
have been of multifold biological and pharmacological
interest. Thus, some derivatives of L-ascorbic acid, e.g., 6bromo-, 6-amino-, and N,N-dimethyl-6-amino-6-deoxy-Lascorbic acid, have been found to inhibit the growth of
certain human malignant tumor cells lines: cervical
carcinoma (HeLa), laryngeal carcinoma (Hep2), and
pancreatic carcinoma (MiaPaCa2). Furthermore, several
nucleosides containing a 5-substituted pyrimidine moiety
have been shown to inhibit growth of the murine mammary
carcinoma (FM3A TK-/HSV 1 TK+) cells transformed with
the herpes simplex virus type 1 (HSV-1) TK gene. Searching
for compounds related to these classes of biologically and
pharmacologically active molecules, we have prepared new
types of molecules containing pyrimidine or purine moieties
N
B n = benzyl
O
F
F
X = Cl
X = NH2
N
O
N
N
F
connected via an acyclic chain to 2,3-dibenzyl-4,5didehydro-5,6-dideoxy-L-ascorbic acid. Raic-Malic et al
synthesized purine derivatives of L-Ascorbic acid [1-(6Chloropurin-9-yl)-2-(2,3-O,O-dibenzyl-2-buten-4-olidylidene
) ethane, 1-(6-Chloropurin-7-yl)-2-(2,3-O,O-dibenzyl-2-buten
-4-olidylidene)ethane,1-[6-(N-Pyrrolyl)
purin-9-yl]-2-(2,3O,O-dibenzyl-2-buten-4-olidylidene)ethane & evaluated
these compounds for their antitumour activity against
malignant tumor cell lines: pancreatic carcinoma
(MiaPaCa2), breast carcinoma (MCF7), cervical carcinoma
(HeLa), laryngeal carcinoma (Hep2), murine leukemia
(L1210/0), murine mammary carcinoma (FM3A), and human
T-lymphocytes (Molt4/C8 and CEM/0)15.
N
R
NH
CO 2Na
N
N
C
H
CO 2H
N
N
Ar
R = H, CH(OH)Me, CH 2CH 2SMe, CH 2CO 2H, CH 2Ph,
CH 2
N NH
Figure 12: New N-(purin-6-yl)-amino acid and -peptide
derivatives
In the similar study, Murti et al synthesized N-9 substituted6-chloropurine derivatives and evaluated these compounds
for their cytotoxic activities against HEp-2 cell line by SRBS
assay. Some of the tested compounds showed moderate
anticancer activity10.
JPSI 1 (2), MARCH – APRIL 2012, 29-34
Sachan Dinesh et al: Biological activities of purine analogues
the 1–5 μM range for most human tumor cell lines. Other
compounds exhibited moderate activity17.
Cl
N
N
Cl
N
N
N
R
Cl
a
Figure 13: N-9 substituted-6-chloropurine derivatives
Table: showing various substitutions for N-9 substituted-6chloropurine derivatives
1
2
3
4
5
6
7
8
9
10
11
12
R
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-NO2
4-NO2
4-NO2
4-OH
4-OH
N
N
Substitutions
R1
H
4-Cl
2-NO2
4F
H
4-Br
3,5- di Cl
4-F
3,5- di Cl
4-Cl
2-NO2
4-Br
R2
H
H
H
H
CH3
H
H
H
H
H
H
H
In the above context, Gordaliza M. et al isolated agelasines,
asmarines and related compounds as natural products having
a hybrid terpene-purine structure from numerous genera of
sponges (Agela sp., Raspailia sp.) and some of these natural
products have an important cytotoxic activity against several
cancer cell lines, including multidrug-resistant ones13.
Phadtare S. et al synthesized a series of twenty four acyclic
unsaturated
2,6-disubstituted
purines
using
2,6dichloropurines and these compounds were evaluated for
their cytotoxic activity against NCI-60 DTP human tumor
cell line at 10 µM concentration. Out of which N9-[(Z)-4'chloro-2'-butenyl-1'-yl]-2,6-dichloropurine,
N9-[(E)-2',3'dibromo-4'-chloro-2'-butenyl-1'-yl]-6-methoxypurine
and
N9-[4'-chloro-2'-butynyl-1'-yl]-6-(4-methoxyphenyl)-purine
exhibited highly potent cytotoxic activity with GI50 values in
N
N
H
H
R1
Compound No.
N
N
R2
OCH 3
OCH 3
Cl
H
N
N
Br
Br
b
N
N
Cl
N
N
c
Cl
Figure 14: acyclic unsaturated 2,6-disubstituted purines
Growth Inhibitors: Recent reviews on the chemotherapy of
Chagas' disease and American cutaneous leishmaniasis have
emphasized the deficiencies of currently available therapeutic
agents and the need for new ones. These diseases are still
important health problems in the Western Hemisphere, while
Trypanosoma rangeli, which is apparently a harmless parasite
of humans and a variety of birds and domestic animals,
infects about 52% of exposed people in endemic areas. Avila
et al reported growth inhibitory effects of six guanine and
guanosine analogs, 3-deazaguanine (compound 1); 3deazaguanosine
(compound
2);
6-aminoallopurinol
(compound 3); 9-I-xylofuranosyl guanine (compound 4); a
ribosylated derivative of compound 3, 6-aminopyrazolo(3,4d)pyrimidin-4-one (compound 5); and 5-aminoformycin B
(compound 6), were tested against some pathogenic members
of the family of American Trypanosomatidae. Compounds 1
and 2 were highly active against Trypanosoma cruzi,
Trypanosoma rangeli, and American Leishmania spp. in in
vitro culture forms. Compound 3 was the most active
compound in vitro, inhibiting all of the American
Trypanosomatidae culture forms tested. It was also highly
inhibitory in mice that were acutely infected with T. cruzi.
Ribosylation of compound 3 resulted in a derivative that
showed decreased inhibitory activity on Trypanosomatidae
multiplication. Compound 6 was highly inhibitory of in vitro
multiplication of American Leishmania and T. rangeli but
had no effect on T. cruzi epimastigotes and on mice that were
acutely infected with T. cruzi. Compound 4 showed only a
slight effect on T. cruzi epimastigotes18.
Antiprotozoal Activity: Gordaliza M. et al isolated
agelasines, asmarines and related compounds as natural
products having a hybrid terpene-purine structure from
numerous genera of sponges (Agela sp., Raspailia sp.) and
some of these natural products have displayed high general
toxicity towards protozoa13.
JPSI 1 (2), MARCH – APRIL 2012, 29-34
Sachan Dinesh et al: Biological activities of purine analogues
H
H
R
R
R
H
a g e la s in e A
a g e la s in e C
a g e la s in e B
H
H
R
R
R
HO
H
HO
a g e la s in e D
H
R
R
R
a g e la s in e K
a g e la s in e J
H
H
N
a g e la s in e I
a g e la s in e H
a g e la s in e L
R
R
O
a g e la s in e E
O
R
1
a g e lin e B , R 1 = H
a g e la s in e G , R 1 = B r
R
a g e la s in e F ( a g e lin e A )
Figure 15: Agelasines, asmarines and related hybrid terpene-purine compounds
CONCLUSION
This review illustrates different types of biological activities
revealed by synthetic compounds having purine ring and its
analogues. Several novel purines have been evaluated for
their biological activities. Biological screening study of
purine analogues show that the compounds exhibit different
physiological activities and can contribute to further
development of medicinal agents. Some natural purine
derivatives have a profound impact on human health. The
biosynthetic engine of Nature produces innumerable purine
derivatives with distinct biological properties that make them
valuable as health products or as structural templates for drug
discovery. Purines and related structures display cytotoxicity
and antiprotozoal, antimicrobial activity. The review
demonstrates that purine and its analogs exhibit some potent
medicinal properties in vitro and in vivo thus suggesting a
new rationale for its use in the management of various
diseases and in maintenance therapy.
ACKNOWLEDGEMENTS
The author would like to express hisr gratitude to the Central
Drug Research Institute for providing sufficient research
papers to prepare this review article. I would also like to
acknowledge my friend Shikha Gangwar for her precious
support for this study.
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Source of support: Nil, Conflict of interest: None Declared
JPSI 1 (2), MARCH – APRIL 2012, 29-34