PRESENTATION ON

SYNTHESIS and BIOLOGICAL

ACTIVITY of TRiAZOLEs

GUIDED BY :DR. SANDEEP K.DIXIT

SUBMITTED BY: YASHI RASTOGI
(M.SC. CHEMISTRY) 2019-20
CONTENT -
1- Introduction.
2-Method of synthesis.
3-Biological activity of Triazoles.
4- Conclusion.
 INTRODUCTION
 The history of hetero-cycles began its journey in the early nineteenth century when
Luigi Brugnatelli first isolated the heterocyclic compound alloxan (2, 4 , 5, 6-
pyrimidinetetrone) in 1818. It is a very important branch of organic chemistry
accounting for nearly one-third of modern publications. In fact, two-thirds of
organic compounds are heterocyclic compounds. A cyclic organic compound having
all carbon atoms in ring formation is referred to as a carbocyclic compound. If at
least one atom other than carbon forms a part of the ring system then it is
designated as a heterocyclic compound. Nitrogen, Oxygen, and Sulfur are the
common hetero atoms but heterocyclic rings containing other hetero atoms are also
widely known. There is a significant and continuous concern in the chemistry of
five-membered N-heterocyclic compounds, mainly tetrazole, triazoles, and their
substituted derivatives. Five-membered N- heterocyclic compounds are important
structural fragments and considered as biologically active compounds. In 1885,
Bladin was the first scientist who gave the name Triazole to the carbon nitrogen ring
system. Triazole, also known as pyrrodiazole, is one of the classes of organic
heterocyclic compounds containing a five membered diunsaturated ring structure
composed of three nitrogen atoms and two carbon atoms at non-adjacent positions.
Structure of Triazoles.
The triazole derivatives and their nucleoside analogs have shown
strong cytotoxicity against several human cancer cells . For
instance, Peng and col. reported two novel N-aryltriazoles as potent
apoptosis-related antiproliferative activity against a drugresistant
pancreatic cancer cell line. It has also been reported that the
biological activity of compounds containing a triazolic ring in their
structure is due to the high dipolar moment of this heterocycle
which allows strong hydrogen bonding interaction with the
biological target. Furthermore, this heterocycle has been reported
to be stable to acidic and basic hydrolysis as well as
reductive/oxidative conditions . On the other hand, it has been
proved that the isoxazoline ring acts as inhibitor of tumor cells and
enhances the antiviral activity of isocarbonucleosides . In addition,
Kamal et al. have recently described a new 3,5-diarylisoxazoline
linked 2,3-dihydroquinazolinone as a good candidate to further
develop potential anticancer agents
Triazole  and their derivatives are of great
importance in medicinal chemistry and can be
used for the synthesis of numerous heterocyclic
compounds with
different biological activities such as antiviral,
antibacterial, antifungal, anti tuberculosis,
anticonvulsant, antidepressant, anti-inflammatory,
anticancer activities, etc
METHOD OF SYNTHESIS
Pellizzari Reaction

 The synthesis of 1,2,4-triazole derivatives by the mixture of amide and acyl

hydrazide is generally referred to as the Pellizzari Reaction. It has been
reported that heating the mixture of formamide and hydrazine hydrochloride
with KOH yield of 1,2,4-triazole.
Einhorn- Brunner Reaction-

The synthesis of 1,2,4-triazoles by condensation

between hydrazines or monosubstituted hydrazine
and diacylamines in the presence of weak acid is
known as the Einhorn–Brunner reaction. For example,
N-formyl benzamide and phenylhydrazine gave 1,5-
diphenyl1,2,4-triazole 5,6
Click Reaction -

The highly controversial force-induced cyclo reversion

of 1,2,3-triazole, its well-known retro-click reaction, is
shown to be possible only for 1,5-substituted triazoles,
but competes with rupture of an adjacent single-bond.
Biological activity of Triazoles.
A-Antibacterial activity –

Synthesis and antibacterial activity of metronidazole-triazole

conjugates have been reported. To study their effect on antibacterial
activity, a total of 21 hybrid compounds were synthesized in a triazole
ring with a different substitution pattern. These compounds are known
to potentiate weak antibacterial activity against Gram-positive and
Gram-negative bacteria. Six compounds showed equivalent or better
antibacterial activity against Gram-negative strains than the reference
compound.
Structure of Metronidazole-
Triazole
B- Antifungal activity-
Fluconazole-based novel simulations containing 1,2,3-triazole
have been designed and synthesized as antifungal agents. Their
antifungal activities are assessed in vitro by measuring minimum
inhibitory concentrations (MICs). The compounds were found to
be more potent against Candida fungal pathogens than control
drugs fluconazole and amphotericin B. The studies presented
here provide a structural modification of fluconazole to give 1,2,3-
trazole containing atoms. Furthermore. these molecules were
analyzed in Swiss mice against the Candida albicans intravenous
challenge in vivo, and antiproliferative activity against human
hepatocellular carcinoma Hep3B and human epithelial carcinoma
A431 was examined. It was found that the fungal load in rats
decreased by 97.4% as a result of the compound and did not show
a profound enhancement effect at low dose (0.001 mg / ml)[9].
Structure of Fluconazole-
C- Anticancer activity-
The compounds were first evaluated at one dose of the primary anticancer assay
towards approximately 60 cell lines (concentration 10−5M). The human tumor
cell lines represent all forms of cancer (such as non-small-cell lung cancer,
colon cancer, breast cancer, ovarian cancer, leukemia, renal cancer, melanoma,
prostate cancer). In the screening protocol, each cell line was inoculated and
pre-incubated for 24–48 h on a microtiter plate. Test agents were then added at
a single concentration and the culture was incubated for an additional 48 h.
The endpoint determinations were made with a protein binding dye,
sulforhodamine B (SRB). The results for each test agent were reported as the
percent growth of the treated cells compared to the untreated control cells. The
preliminary screening results are shown in Table 1. The results for each
compound are reported as the percent growth (GP). Range of growth (%)
shows the lowest and the highest growth
that was found among different cancer cell lines
Some anticancer Drugs-
 Conclusion
Triazoles have received considerable attention in the medical field due
to their unique structures and properties. Triazoles derivatives are of
great importance in chemistry and serve as a good agent for scientists
working in this field. The various synthetic methods discussed here
help to develop various new compounds that contain triazoles moiety,
which are better in terms of efficacy and less toxicity, predicting
further activity of triazole for treatment-challenging diseases in the
field of medicine. So it can be seen from the literature review that the
triazole ring with heterocyclic system has extensive medicinal
applications. The triazole ring has been explored in the past years by
studying all the derivatives that show different types OF activity, and is
still being used for the future development of new drugs against many
pathological conditions.