Biological Potentials of Biological Active Triazole Derivatives: A Short Review

Heterocycles make up an exceedingly important class of compounds. In fact, more than half of all known organic compounds are heterocycles. Many natural drugs are heterocyclic in nature. Many synthetic drugs are also heterocycles. Heterocyclic compounds occupy a central position among those molecules that make life possible. Heterocycles have been explored for developing pharmaceutically important molecules. In recent decades there has been constant interest in the chemistry of azoles because more than hundred azole derivatives are used today as drugs. Azoles are heterocyclic compounds characterized by a five-membered ring which contains an atom of nitrogen and at least one other noncarbon atom, nitrogen, sulfur or oxygen. These compounds are aromatic and have two double bonds.


Introduction
Heterocycles make up an exceedingly important class of compounds. In fact, more than half of all known organic compounds are heterocycles. Many natural drugs are heterocyclic in nature. Many synthetic drugs are also heterocycles. Heterocyclic compounds occupy a central position among those molecules that make life possible. Heterocycles have been explored for developing pharmaceutically important molecules. In recent decades there has been constant interest in the chemistry of azoles because more than hundred azole derivatives are used today as drugs. Azoles are heterocyclic compounds characterized by a five-membered ring which contains an atom of nitrogen and at least one other noncarbon atom, nitrogen, sulfur or oxygen. These compounds are aromatic and have two double bonds.

Triazoles and related compounds
Five inembered aromatic rings with three nitrogen atoms are called triazoles. The two possible combinations of the five atoms account for vicinal(v) and syrnmetrical(s) triazoles In chemical absracts, v-triazoles is also listed as 1H-l,2,3-t-riazoie or pyrrodiazole and 2H-l,2,3-triazole or pyrrodiazole. The pyrrodiazole was occasionally used to designate triazole. The term osotriazole refers to derivatives of 2H-1,2,3-triazole particularly those prepared from osazones (Schemes 1 and 2).
Heterocyclic compounds bearing a symmetrical triazoles moiety have been reported to have a broad spectrum of pharmacological activities (Schemes 3-9).
Triazoles have been reported to possess wide variety of biological activity. Some of these activities are mentioned here.

Abstract
Triazole is a versatile lead molecule for designing potential bioactive agents. The triazole derivatives have been found to exhibit diverse biological activities such as anti-fungal, antibacterial, antitubercular, anti-inflammatory, analgesic, anticancer, antiviral and other biological properties. Consequently, they have attracted increasing attention in the field of drug discovery. Similarly, oxazoles and their fused heterocyclic derivatives have received considerable attention owing to their effective medicinal importance. These compounds are dual inhibitors of cyclooxygenase and 5-Lox. Among these 2c is more active (80%) than 2a and 2b.
Compounds of 3a series exhibited promising antiflammatory activity (40, 51 and 52%) compared to phenylbutazone at a dose of 100 mg/kg body wt. These compounds also showed mild to moderate analgene activity (4-40%) in comparison to aspirin (60%) at 100 mg/ kg body wt. Some of these compounds at a dose of mg/kg, -i.v also produced rapid fall in blood pressure followed by quick recovery whereas hydrakizine at 2 mg/kg i.v. produced gradual and transient fail in the blood pressure (42 mm Hg) with long duration and slow recovery.
All these compounds were active against S. aureus, E. coli, S. typhi, and P. aeruginosa except 13b, which was inactive against Pseudmonas.
Antifungal activity: Most of the recent clinically used anti-fungal drugs contain triazoie nucleus, none of the drug used today are from other azoles like oxadiazole, pyrazine, and triazine. The main drawback of triiizoles is CYP 450 Isoform inhibition selectivity. This results in many drug interactions when given concomitantly with certain medications also metabolized by this CYP Isoform. For example, fluconazole inhibits the metabolism of warfarin leading to increase in bleeding time. Fluconazole also decrease the metabolism of the CYP 2C9 substrate phenytoin, an anti-epileptic drug with a narrow therapeutic index. On the basis of above facts, different types of azoles are still in progress to get a better drug, some are given as follows. Antifungal activity of 2-aryl-5-(3,5-diphenylpyrazole4-yl oxymethyl)-1,3,4-oxadiazoles (16ac) [14] (Scheme 24).
Compounds 17b, 17e and 17h have very strong activity against Aspergillus niger and Peuicilliiini cilrimun at 1000, 100 and l0 ppm concentration. All these three compounds have either 2-Cl. 4-Cl or 4-OCH 3 groups (electron donar group) in their structure.
The compounds 28a and 28c showed significant antifungal activity against A. niger and C. albicans at 1000 g/ml concentrartion.
Ravuconazole: It is found to be more potent thati flucofiazole and itraconazole aginst clinical isolates of Crypiococciis deofonnans.    Triazoles have been reported to possess wide variety of biological activity [28,29].