816429-52-4Relevant academic research and scientific papers
Optimization of pyrazole-based compounds with 1,2,4-triazole-3-thiol moiety as selective COX-2 inhibitors cardioprotective drug candidates: Design, synthesis, cyclooxygenase inhibition, anti-inflammatory, ulcerogenicity, cardiovascular evaluation, and molecular modeling studies
Abdellatif, Khaled R.A.,Abdelall, Eman K.A.,Elshemy, Heba A.H.,Philoppes, John N.,Hassanein, Emad H.M.,Kahk, Nesma M.
, (2021)
The cardiovascular side effects associated with COX-2 selective drugs were the worst for coxibs leading to their withdrawal from the market a few years after their discovery. Therefore, the design of new series of pyrazole (4a,b 5a,b, 7a,b, 9a,b, 10a-h, and 11a-f) substituted with a triazole moiety as selective COX-2 inhibitors with cardioprotective effect was aimed in this paper. The target compounds were prepared and evaluated in-vitro against COX-1 and COX-2 enzymes. Compound 5-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-4H-1,2,4-triazole-3-thiol (7a) showed the highest selectivity towards COX-2 enzyme (S.I. = 27.56) and was the most active anti-inflammatory agent. Interestingly, its cardiovascular profile showed the cardiac biomarkers (ALP, AST, CK-MB, and LDH), as well as inflammatory cytokines named (TNF-α and IL-6) nearly similar to the control. Besides, a histopathological study of the heart muscle and the stomach was also included. The results confirmed that compound 7a has a more favorable cardio profile than celecoxib. Moreover, docking simulation for the most selective compounds 4b, 7a, 10e, 11c, and 11e inside COX-2 active site was performed to explain their binding mode. Finally, an ADME study was applied and proved the promising activity of the new compounds as a new oral anti-inflammatory agent. In conclusion, the newly developed compound 7a represents a potential selective COX-2 NSAID candidate with minimum cardiovascular risks.
Synthesis, biological evaluation and docking studies of a new series of tris-heterocycles containing pyrazole, triazole and oxadiazole
Kumar, Gaddam Rajesh,Shankar, Kurre,Reddy, Cherkupally Sanjeeva
, p. 687 - 699 (2019/05/22)
A new series of 3-aryl/hetaryl-6-(5-methyl-l-phenyl-lH-pyrazol-4-yl)-[l,2,4]triazolo[3,4-b][l,3,4]oxadiazoles 7a-j have been synthesized, characterized by spectral means, and evaluated for their antimicrobial and antioxidant properties. Amongst the screened compounds 7a-j, the triazole moiety bearing electron-withdrawing group on the 4th position of phenyl viz. 4-chlorophenyl 7c, 4-nitrophenyl 7f and 2,4-difluorophenyl 7h exhibit excellent antibacterial activity towards all the tested bacteria viz. Staphylococcus aureus. Bacillus licheniformis, Pseudomonas aeruginosa and Escherichia coli. On the other hand, triazole moiety bearing electron-donating group on the 4th position of phenyl viz. 4-hydroxyphenyl 7d, 4-methoxy-phenyl 7e and 4-aminophenyl 7g show prominent antifungal activity towards the tested fungi viz. Candida albicans and Fusarium oxysporum. These results are supported by molecular docking studies and through binding interactions as well. Antioxidant studies reveal that the compounds in which the triazole moiety bearing phenyl 7a, 4-methoxyphenyl 7e, 2,4-difluorophenyl 7h and 3-pyridyl 7j is present on the 4th position, display significant antioxidant "' properties. In brief, most of the newly synthesized compounds have emerged as potential antimicrobial and antioxidant agents for further development.
Synthesis and antibacterial activity of di-heteryl substitued [1,2,4]triazolo [3,4-b] [1,3,4]thiadiazoles
Sanjeeva Reddy,Vani Devi,Sunitha,Kalyani,Nagaraj
, p. 590 - 597 (2017/01/18)
A new series of 3-(5-methyl-1-phenyl-1H-4-pyrazolyl)-6-(5-methyl-1-aryl-1H-1,2,3-triazol-4-yl)[1,2,4]triazolo [3,4-b][1,3,4]thiadiazoles 12a-j have been prepared and assayed for their antibacterial activity against human pathogenic Gram-positive bacteria viz., Staphylococcus aureus, Bacillus subtilis and Gram-negative Escherichia coli. Among the screened compounds 12b, 12c and 12f, in which phenyl ring of triazole moiety bear 4-chloro, 4-nitro and 4-fluoro substituents respectively, showed high activity against all the micro-organisms employed. The activities of these compounds are almost equal to the standards.
Synthesis and antibacterial activity of N-substituted-[1,2,4]triazoles and 1,2,4-Triazole[3,4-b][1,3,4]thiadiazines
Sanjeeva Reddy,Sanjeeva Rao,Sunitha,Nagaraj
, p. 1283 - 1289 (2015/11/25)
New series of N-[3-(5-methyl-1-phenyl-1H-4-pyrazolyl)-5- sulfanyl-4H-1,2,4-Triazol-4-yl]-N'-Arylthiourea derivatives 8a-e and 3-(5-methyl-1-phenyl-1H-4-pyrazolyl)-6-Aryl-7H-[1,2,4] triazolo[3,4- b][1,3,4]thiadiazines 9a-e have been prepared and screened for their antibacterial activity against four human pathogenic bacteria, Escherichia coli, Klebseilla pneumoniae, Shigella dysentriae and Shigella flexnei. Among the screened, compounds 8b, 8c and 8e, in which phenyl ring of isothiocyanate moiety bear 3-fluoro, 4-fluoro and 4-bromo substituents respectively, show high activity against all the micro-organisms employed. The compound 9c is highly active against all the test organisms employed. The zone of inhibition is more than what is found for the standard drug neomycin, and almost equal to the standard drug streptomycin.
Synthesis and antimicrobial activity of linked heterocyclics containing pyrazole and oxadiazoles
Reddy, Ch. Sanjeeva,Rao, L. Sanjeeva,Devi, M. Vani,Nagaraj
, p. 1038 - 1043 (2013/01/15)
A new series of 3-(arylaminomethyl)-5-(5-methyl-1-phenyl-1H-4-pyrazolyl)-2, 3-dihydro-1,3,4-oxadiazole-2-thiones 6a-j has been synthesized by the reaction of 5-(5-methyl-1-phenyl-1H-4-pyrazolyl)-1,3,4-oxadiazol-2-ylhydrosulfide 5 with formaldehyde and corresponding anilines. The chemical structures of newly synthesized compounds were elucidated by IR, 1H, 13C-NMR, MS, and elemental analyses. The compounds 6a-j were evaluated for their antibacterial activity against three representative Gram positive bacteria viz. Bacillus subtilis (MTCC 441), Bacillus sphaericus (MTCC 11) and Staphylococcus aureus (MTCC 96), and three Gram negative bacteria viz. Pseudomonas aeruginosa (MTCC 741), Klobsinella aerogenes (MTCC 39) and Chromobacterium violaceum. Among the screened 6b, 6d, 6i, and 6j in which oxadiazole moiety bearing 4-fluoroanilinomethyl, 4-chloroanilinomethyl, 2-trifluoromethylanilinomethyl, and 2,5-difluoroanilinomethyl groups, respectively, showed high activity against all the microorganisms used. In addition these compounds were also screened for their antifungal activity against four fungal organisms viz. Candida albicans (ATCC 10231), Aspergillus fumigatus (HIC 6094), Trichophyton rubrum (IFO 9185), and Trichophyton mentagrophytes (IFO 40996). Most of these new compounds showed appreciable activity against test fungi, and emerged as potential molecules for further development.
Synthesis of new 1,2,4-triazole[3,4-b][1,3,4]thiadiazoles bearing pyrazole as potent antimicrobial agents
Sanjeeva Reddy, Cherkupally,Sanjeeva Rao, Lade,Rajesh Kumar, Gaddam,Nagaraj, Adki
experimental part, p. 1328 - 1331 (2010/12/18)
A new series of 6-(aryl/heteryl)-3-(5-methyl-1-phenyl-1H-4-pyrazolyl)[1,2, 4]triazolo[3,4-b][1,3,4]thiadiazoles (7a-j) has been synthesized by the reaction of 4-amino-5-(5-methyl-1-phenyl-1H-4-pyrazolyl)-4H-1,2,4-triazol-3-yl- hydrosulfide (6) with POCl3 and the corresponding aryl/heteryl carboxylic acid, in ethanol at reflux temperature for 12 h. All the synthesized compounds were tested for in vitro activities against certain strains of bacteria such as Staphylococcus aureus, Bacillus subtilis, Escherichia coli and fungi such as Aspergillus niger, Aspergillus nodulans, Alternaria alternate. Compounds having 4-chlorophenyl (7d), 4-aminophenyl (7f), 4-nitrophenyl (7h) and 3-pyridyl (7i) substituents at 6-position of thiadiazole ring, showed marked inhibition of bacterial and fungal growth nearly equal to the standards. The other new compounds also showed appreciable activity against the test bacteria and fungi.
