This document provides an overview of 1,2,3-triazoles and their biological activities. It discusses various synthetic strategies for producing 1,2,3-triazoles, including Huisgen cycloaddition and palladium-catalyzed reactions. The document then summarizes research on the anticancer, anti-inflammatory, antitubercular, antiviral, and antibacterial activities of 1,2,3-triazole derivatives, noting several potent compounds and their mechanisms of action.

1. 1,2,3-Triazole
Table Of Contents
1.Introduction .................…………………….........[2-4]
2.Synthetic strategies of 1,2,3-triazoles …..........[5-8]
3.Anticancer Activity of 1,2,3-triazoles ……......[9-11]
4. Anti-inflammatory activity of 1,2,3-triazoles.[11-12]
5. Anti-tubercular activity of 1,2,3-triazoles ….[12-13]
6. Antiviral activity of 1,2,3-triazoles .....….........[14-15]
7. Anti-bacterial activity of 1,2,3-triazoles ....... [16]
8. References ……………………………….……..[17-23]

2. 2
1,2,3-Triazole
◘ Abstract :
Triazole was first synthesized over a century ago, but still attracts attention of chemists,
biologists, technologists and other specialists , 1,2,3-Triazole is one of a pair of isomeric
chemical compounds with molecular formula C2H3N3, called triazoles, which have a
five-membered ring of two carbon atoms and three nitrogen atoms. 1,2,3-Triazole is a
basic aromatic heterocycle , Despite a significant work on 1, 2, 3-triazoles, continuous
efforts are still being made to identify novel heterocyclic compounds with potent
bioactivities , This research throws light on the detailed synthetic approaches which
have been used for the synthesis of triazoles since the early development in the area of
triazole chemistry. This has been followed by the in depth analysis of the triazoles with respect to their
medicinal significance.
♦ 1. Introduction
There are many heterocyclic ring structures, which have been designed [1] in such a way that their binding
efficiency with the receptor increases after structural modifications [2]. This medicinal chemistry is a boon
to the researchers and provides long-term advancement in the medical field [3]. One of the motif is triazoles,
which have been explored widely and still its scope is inevitable. Triazoles are heterocyclic organic
compounds containing five-membered ring with three nitrogen and two carbon atoms. Two isomeric forms
of triazoles are existednamely 1,2,3-triazole and 1,2,4-triazole [4]. Generally, 1,2,3-triazoles are further
subdivided into three main class, namely, monocyclic 1,2,3-triazoles, benzotriazoles and 1,2,3-triazolium
salts as depicted in Fig. 1.

3. 3
• Monocyclic 1,2,3-triazoles and benzotriazoles are remarkably stable
towards hydrolysis, oxidative/reductive conditions, and enzymatic
degradation but reductive cleavage occurs under forcing conditions
leading to the formation of triazolium salts [5,6].
• These motifs are effective amide surrogates in bioactive molecules
because of their strong dipole moments. Triazoles can also be used as a
linker and show bioisosteric effects on peptide linkage, aromatic ring,
double bonds and an imidazole ring. Some unique features like
hydrogen bond formation, dipole-dipole and π stacking interactions of
triazole compounds have increased their importance in the field of
medicinal chemistry as they bind with the biological target with high
affinity due to their improved solubility. In general, the molecular
specifications of the 1,4-disubstituted 1,2,3-triazoles are somewhat
similar to amide bonds in terms of distance and planarity clearly shown
in Fig. 2 [7–12].

4. 4
The 1,2,3-triazolebased heterocycles have been well exploited
for the generationof many medicinal scaffolds exhibitinganti-
HIV, anticancer,antibacterialactivities,etc.[13–18].
Numerous compounds bearing this moiety are also well
acknowledgedfor therapeuticeffects elucidatedin Fig. 3.
There are numerous amount of biologically active molecules containing 1,2,3-
triazole motif and were synthesized well before the ‘click chemistry’ approach
became popular. A few examples are shown in Fig. 3. The 1,2,3-triazole moiety
also serves as key synthetic intermediates in many industrial applications such as
agrochemicals [19–21], corrosion inhibitors [22,23], additives [24,25],
supramolecular chemistry [26,27], dendrimers, polymers [28–31], liquid crystals
[32–34], photostabilizers [35–37], pigments [38–41] and metal chelators [42–44].

5. 5
2. Synthetic strategies of 1,2,3-Triazoles
• 1,2,3-Triazole ring system has been a subject of intense research due to its
versatile potential to interact with diverse biological systems. In recent
years, many synthetic methodologies have been developed for the synthesis
of this ring system .
♦ Methods for the synthesis of 1, 2, 3-triazoles
Scheme 1
The most popular reaction that has been adapted to produce the 1, 2, 3-
triazole moiety is the 1, 3-dipolar cycloaddition also known as Huisgen
cycloaddition, between an azide and a terminal alkyne. Although this
reaction was discovered at the start of the 20th century, its detailed
mechanism was described by Huisgen in the 1960s [45].
This reaction is catalysed by the copper (I) metal and thus most often carried
out in the presence of copper (II) salts e.g. copper sulfate pentahydrate [46]
or copper acetate [47] using sodium ascorbate or metallic copper as a
reducing agent which reduces the copper (II) to copper (I). The solvent used
for this reaction contains a mixture of tert-butanol and water. By using this
solvent system the requirement of a base to generate copper acetylide
species is eliminated and the same can be used for the lipophilic compounds.

6. 6
Scheme 2
A palladium catalysed synthesis of 1, 2, 3-triazoles from alkenyl halides and
sodium azides added a new chapter in the Palladium chemistry [48].
Scheme 3
The terminal alkynes react with a mixture of benzyl or alkyl halides with
sodium azide in ethanol to produce 1, 4- disubstituted 1, 2, 3-triazoles in
good yields [49]. It is catalysed by copper immobilized on 3-aminopropyl
functionalised silica gel.
Scheme 4
An efficient one pot synthesis of 1, 2, 3-triazole linked glycoconjugates
involving 1, 3-dipolar cycloaddition in presence of Cu (I) as a catalyst has
been reported [50]. It is an easy method to prepare neoglycoconjugates
derived from unprotected saccharides or peracetylated saccharides.

7. 7
Scheme 5
Pankaja synthesized a family of closely related 1, 2, 3- triazoles as
anticonvulsant agents in which the dicarboximide moiety was lacking from
the triazole ring, unlike the traditional anticonvulsant agents [51].
Scheme 6
Terminal alkyne on reaction with iodobenzene and mixture of sodium azide,
cuprous iodide and sodium ascorbate gives 1, 2, 3-triazole [52].
Scheme 7
Primary aliphatic amines undergo diazo transfer to form azides which are
converted into 1, 2, 3-triazoles under appropriate reaction conditions [53].

8. 8
Scheme 8
Non-fluorescent 3-azide coumarins can be converted into fluorogenic probes
by reacting them with alkynes. This method is used to generate fluorescent
DNA probes used in the molecular biology [54].
Scheme 9
The organic azides undergo cycloaddition with immobilized alkynes on
polystyrene resins resulting in the formation of 1, 2, 3-triazoles [55].
Scheme 10
Condensed 1, 2, 3-triazoles can be synthesized by the oxidation of arylazo
heterocycles having an amino group in the ortho position [56].

9. 9
3. Anticancer Activity of 1,2,3 Triazoles
The discovery of new drugs for cancer therapy is one of the medicinal chemistry’s most
investigated areas because the global prevalence of this disease continues to grow. The greatest
challenge for scientists in this area is to develop new drugs that are more effective and have lower
toxicity. Selectivity is the dilemma in cancer therapy for the achievement of drug delivery to a
localized tumor and for an even
distribution throughout the body, including the tumor tissues. Other challenges in the treatment of
cancer using chemotherapy include drugs with short half-lives in blood circulation, fewer side
effects, and effectiveness. The development of research in this area aims to attack the problem
from different angles, such as chemotherapy conjugated with drug carriers to act as magic bullets
or to enhance
distribution of the drug molecule in the body [57].
Recently, several triazoles have been found to have activities against several cancer cell lines [58,
59]. The researchers are focusing their efforts on the anticancer activity [60–61] in compound
hybrids of 1,2,3-1H-triazole tethered with the β-lactam (115), triterpenoid (116), and chalcone
(117, 118) moieties that were evaluated against several cancer cell lines and were selective to A-
549(lung)
[62], chalcone-pyrrolo[2,1-c] [1,4]benzodiazepine conjugates containing alkane spacers with
promising in vitro anticancer activity in concentrations ranging from <0.1–2.92 μM [63]. These
compounds have also been screened on the apoptosis enzymes that regulate cellular programmed
cell death of unnecessary cells as shown in Fig. A [64, 65].

10. 10
• Drugs used therapeutically for other diseases canserve as models in the search for new lead compounds.
Revankar and coworkers synthesized a series of six analogues of the antiviral drug ribavirin (121–126)
containing 1,2,3-2H-triazoles and studied them as inhibitors of the tumor cell line HL-60 [66]. The
derivatives were obtained by a synthetic sequence (Scheme 11) that begins with a condensation
reaction between the triazole compound (119) and ribofuranoside (120) catalyzed.

11. 11
by a Lewis acid, trimethylsilyl triflate. The product 121 is then converted by several reactions to the
nucleosides 122–126. 126 inhibited HL-60 at a level that was 50% of the inhibitory effect of ribavirin
(Scheme B).
Metal complexes are widely used in chemistry and in many treatments of diseases, including cancer
chemotherapy. For example, organotin (IV) carboxylates are used in many applications in chemistry and
biology, such as antitumor activity [67].
Tiam and coworkers synthesized three triorganotin 2-phenyl-1,2,3-triazole-4-carboxylates (127a–c), and a
bioassay showed that these compounds have good antitumor activity against three human tumor cell lines
(HeLa, CoLo205, and MCF-7) [68]. In addition, platinum complexes are widely used in cancer
chemotherapy. For example, cisplatin, approved by the FDA in 1978, and carboplatin [69], are the most
commonly used anticancer platinum complexes in the clinical treatment of testicular and ovarian malignant
tumors [70–72], and their mechanism of action is the induction of apoptosis [73, 74].
Considering these findings, Reedijk and coworkers [75] synthesized two binuclear platinum complexes [76]
with triazoles as ligands. The compounds 130 and 131 demonstrated to have better anticancer activity (18
times more cytotoxic)
than cisplatin against tumor cell lines (acute lymphoblastic leukemia cisplatin sensitive and cisplatin-
resistant) (Fig. A).
Girard and coworkers [77, 78] synthesized mono- and bis-1,2,3-triazoles from bis-alkynes to be tested
against the human tumor strain B16 (murine melanoma cell line) that is highly malignant, metastatic, and
chemoresistant [79–81].
4. Anti-inflammatory activity of 1,2,3-triazoles
• Haider et al have synthesized a library of benzoxazolinone based1, 2, 3-triazoles using
click chemistry approachand screenedthem for their in vitro and in vivo anti-inflammatory
activity. The compound 1 exhibited potent in vivo anti-inflammatory activity
,The compound 2 exhibited significantTNF-α inhibitory activity [82].
• Shafi et al have synthesized novel bis-heterocyclesencompassing 2-mercapto benzothiazole
and 1, 2, 3- triazoles and evaluated them for their anti-inflammatory activity by using
biochemicalcyclooxygenase(COX) activity assays [83].

12. 12
• Assis et al have synthesized 1, 2, 3-triazole based phthalimide
derivatives by the 1,3-dipolar cycloaddition reaction of N-(azido-
alkyl)phthalimides with terminal alkynes and screened them for their
anti-inflammatory activity.[84]
• Silva et al carried out the synthesis and anti-inflammatory activity of novel
glucosyl triazoles from a reaction of 2, 3, 4, 6-tetra-O-acetyl-β-D-glucopyranosyl
azide and terminal alkynes using ultrasound energy. The compound 5 exhibited
potent anti-inflammatory activity [85]
5. Anti-tubercular activity of 1,2,3-triazoles
• Somu et al carried out the synthesis of the compound 6 which was found to be
the inhibitor of Mycobacterium tuberculosis. Its activity is due to the inhibition of
the adenylate forming enzyme MbtA, which is involved in biosynthesis of the
mycobactins.[86]

13. 13
• Yempala et al have synthesized a series of novel dibenzofuran based 1, 2, 3-
triazole derivatives using click chemistry approach and screened them for their
in vitro anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv.
The compound 7 was found to be most potent antitubercular agent with lowest
cytotoxicity against the HEK-293T cell line.[87]
• Menendez et al have synthesized a series of 1,2,3- triazoles as inhibitors of
Mycobacterium tuberculosis H37Rv. Compounds 8 and 9 were found to be good
inhibitors of Mycobacterium tuberculosis.[88]
• Menendez et al have synthesized and screened the phenethyl based 1, 2, 3-
triazoles as the inhibitors of Mycobacterium tuberculosis H37Rv. The compound
10 was found to exhibit a potent antitubercular activity.[89]

14. 14
6. Antiviral activity of 1,2,3-triazoles
• Piotrowska et al have reported the synthesis and the antiviral activity of novel
isoxazolidine nucleotide analogues with a 1, 2, 3-triazole linker.
The synthesized 1, 2, 3-triazole based isoxazolidine phosphonates were evaluated
for their in vitro activity against a variety of DNA and RNA viruses.[90]
• He et al have carried out the synthesis of novel 1, 2, 3- triazole-containing
derivatives of rupestonic acid and screened them for their antiviral activity
against influenza virus using oseltamivir and ribavirin as the standard drug.[91]

15. 15
• Jorda˜o et al have synthesized N-amino-1,2,3-triazole derivatives i.e. 1-(4-
substituted-phenylamino)-5-methyl- 1H-[1,2,3]-triazole-4-carboxylic acid
hydrazides and 1- (substitutedphenylamino)-5-methyl-1H-[1,2,3]-triazole-4-
carboxylic acid ethyl esters and screened them against Cantagalo virus
replication. This compound exhibited an inhibition of 55.70% on the virus
progeny production.[92]
• Silva et al have carried out the synthesis and the in vitro HIV-RT inhibitory
activity of 1-benzyl-1H-1, 2, 3-triazole derivatives of carbohydrates (compound A
and B ) .[93]

16. 16
7. Anti-bacterial activity of 1,2,3-triazoles
• Phillips et al have synthesized novel 5-(4-methyl-1, 2, 3- triazole)methyl
oxazolidinones and screened them for their in vitro antibacterial activity against
the Gram-positive and Gram-negative bacteria using linezolid and vancomycin
as standard.[94]
• Wang et al have synthesized sulfanilamide based 1, 2, 3- triazoles and screened
them for their in vitro antibacterial (S. aureus, B. subtilis, E. coli, P. aeruginosa)
and antifungal (C. albicans and C. mycoderma) activities.[95]

17. 17
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