*Corresponding Author E-mail: rushikesh.sonawane509@gmail.com
ABSTRACT:
KEYWORDS: Triazolo thiadiazols, 1,3,4-thiadiazole, Scaffold, Pharmacological Screening.
INTRODUCTION:
Heterocyclic chemistry is one of the leading active fields of synthetic organic chemistry research. Thiadiazole are most active Class with heterocyclic scaffolding for their interesting pharmacological and synthetic applications. Thiadiazole containing both nitrogen and sulfur atoms as part of the Five-membered aromatic ring. Most thermal stable isomers are 1,3,4-thidiazoleas a heterocyclic scaffold. Roused by the references and continuation of our research. Its derivatives have Several therapeutic applications in antimicrobial, anticancer, antitubercular and anti- inflammatory activities.[1]
The existence of the -N=C-S moiety in thiadiazole ring induces the mentioned multiple activities. Aromaticity of thiadiazol put to low toxicity and in vivo durability[2]
The activity of substituted aryl acids linked with thiadiazol and such derivatives They're well known for medicinal importance and are recognized their use as pharmacological activity. The Synthetic and biological Significance places Nitrogen group in an Medicinal chemistry research and thiadiazole ring which containing two nitrogen and one sulfur atoms in five membered ring possessing a diversity of useful Pharmacological effects.
Thiadiazole nucleus is an active and pivotal area of research in chemistry. Substitution at thiadiazole ring is a challenging approach to obtain agents with enhance potency and less toxicity. Thiadiazole is a importance scaffold for diverse biological potential.
Thiadiazole nucleus is an active and pivotal area of research in chemistry. Substitution at The ring of thiadiazole is a challenging approach to obtain agents with enhance potency and less toxicity. Thiadiazole is a importance scaffold for diverse biological potential.
Thiazole is essential sulfur and nitrogen containing compounds known to be a unique scaffold that having potential anti-inflammatory, anticancer activity.
IMPORTANCE OF HETEROCYLIC CHEMISTRY
Heterocyclic compounds are widely distributed in nature which are essential to life and industry also. Many heterocyclic compounds are biosynthesized by plants animals and are biologically active.over millions of year these organism have been under intense evolutionary pressure,and their metabolites may be used to advantages:for example, as toxinstowards off predators or as coloring agents to attract mates or pollinating insects. Some heterocycles are crucial, such as haem derivatives in blood and chlorophylls necessary for photosynthesis. Similarly, the paired bases located in RNA and DNA are heterocycles, as is the sugar that provides the framework in association with phosphate and defines the topology of these nucleic acids.[3]
They are still a major attraction for the medicinal and synthetic chemists for discovery of drugs and drug intermediates. Extensive work It was carried out on several heterocycles containing nitrogen atom either fused with other heterocycles or substituted by various important role. Many of the drug Currently available mostly on market contain several heterocycles, with nitrogen atom, as a major backbone having potential biological activity.[4]
DESIGN STRATEGY FOR TARGET COMPOUNDS:
ANALGESIC AND ANTI-INFLAMMATORY ACTIVITY
Mathew et al.5 Have synthesized several 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole and their dihydro analogues and evaluated them for anti-inflammatory and analgesic activity. Among the synthesized compounds, compound 1 showed good Anti-inflammatory and analgesic potential.
Currently available non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, flurbiprofen, fenbufen and naproxen exhibit gastric toxicity. Literature survey showed that the alteration of carboxyl function of representative NSAIDs resulted in enhanced anti-inflammatory activity with reduced colitis impact. Containing compounds 1,2,4-triazole and 1,3,4-thiadiazole nuclei has significant anti-inflammatory efficacy with lowered GI toxicity. To reduce the toxicity. Amir et al6. The carboxylic acid group of 2-(4-isobutylphenyl) propanoic acid and biphenyl-4-yloxy acetic acid has been substituted by a hybrid system of triazole and thiadiazole nucleus. To give a compact and planar structure to its ring. It was interesting to note that seven cyclized compounds 2a, 2b, 3a, 3b, 4a, 4b and 4c were found to have anti-inflammatory properties comparable to their standard reference drugs ibuprofen and flurbiprofen. When these compounds were subjected to analgesic activity by the tail-immersion method in mice, all compounds exhibited moderate to good activity. These compounds were also tested for antiulcer activity and lipid peroxidation and showed a superior GI safety profile and reduced lipid peroxidation compared with ibuprofen and flurbiprofen.
2a, R= 2-aminophenyl, 2b, R= 4-aminophenyl
3a, R =CH3—CH2—CH2—R 3b, R = phenyl
2c, R= 2-chlorophenyl, 2d, R= 4-chlorophenyl
3c, R= 4-fluorophenyl
found that one of the thiadiazol derivative, namely 3-(2-chlorophenyl)-6-[(E)-2-phenylethenyl] [1,2,4] triazolo [3,4-b][1,3,4] thiadiazol showed (36%) of inhibition against Mycobacterium tuberculosis.Further, they found that compound 5 The highest inhibitory activity was shown (41%) of inhibition against in vitro growing Mycobacterium tuberculosis.
So synthesized one of the thiadiazole derivative, namely3-(2-chlorophenyl)-6-(3,5-dinitrophenyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole showed 41% of inhibition against Mycobacterium tuberculosis.
ANTI-NEOPLASTIC ACTIVITY:-
Yang et al.7 Synthesized a series of 1,3,4-thiadiazole amide cinnamic derivatives and evaluated their inhibiting tubulin polymerization activity. Among Synthesized compounds, 6a, have been found to be the most potent compounds which mostly inhibit growth of MCF-7 and A549 cell lines with IC50 values of 0.28 and 0.52 μg/mL. respectively. Compound 6a Significant inhibitory activity of tubulin polymerization (IC50 = 1.16 μg/mL) was shown. The docking simulation was performed to determine the probable binding model.
found that one of the thiadiazol derivative, namely 3-(2-chlorophenyl)-6-(3,5-dinitrophenyl) [1,2,4] triazolo [3,4-b] [1,3,4] thiadiazol showed 39% of inhibition Examine by Egg protein denaturation method Further, they found that compound 8 The highest inhibitory activity has been shown (49%) of inhibition against in vitro Egg protein denaturation method.
So synthesized one of the thiadiazol derivative, namely 3-(2-chlorophenyl)-6-(3-nitrophenyl) [1,2,4] triazolo [3,4-b] [1,3,4] thiadiazol showed 49% of inhibition against in vitro Egg protein denaturation method.
CONCLUSION:
In this work, 1,3,4-thiadiazole compounds derived from substituted aromatic acid were obtained through the cyclization reactionGives some basic chemistry of heterocyclic compounds specially thiadiazol scaffold. Synthesized thiadiazol investigated for their analgesic, anti-inflammatory, anti-microbial and anti-cancer activities. Some of the tested compounds were moderate. and promising antimicrobial activity, anti-inflammatory activities, anti-microbial activities and antitumor activities.
REFERENCES: -
1. Halit M, Hasan Y, Hanan A S, New 1,3,4-thiadiazoles based on thiophene-2- carboxylic acid synthesis, characterization and antimicrobial activities. Journal of Molecular Structure. 2019; 1203: 1-30.
2. Haider S, Alam MS, Hamid H, 1, 3, 4-thiadiazoles a potent multi targeted pharmacological scaffold. European Journal of Medicinal Chemistry. 2015; 92: 156- 77.
Received on 24.02.2020 Modified on 19.04.2020
Accepted on 29.06.2020 ©AJRC All right reserved
Asian Journal of Research in Chemistry. 2021; 14(3):217-220.
DOI: 10.52711/0974-4150.2021.00038