37545-39-4Relevant articles and documents
Antileishmanial potential of fused 5-(pyrazin-2-yl)-4H-1,2,4-triazole-3-thiols: Synthesis, biological evaluations and computational studies
Patil, Sanjeev R.,Asrondkar, Ashish,Patil, Vrushali,Sangshetti, Jaiprakash N.,Kalam Khan, Firoz A.,Damale, Manoj G.,Patil, Rajendra H.,Bobade, Anil S.,Shinde, Devanand B.
, p. 3845 - 3850 (2017)
A series of newer 1,2,4-triazole-3-thiol derivatives 5(a–m) and 6(a–i) containing a triazole fused with pyrazine moiety of pharmacological significance have been synthesized. All the synthesized compounds were screened for their in vitro antileishmanial and antioxidant activities. Compounds 5f (IC50?=?79.0?μM) and 6f (IC50?=?79.0?μM) were shown significant antileishmanial activity when compared with standard sodium stibogluconate (IC50?=?490.0?μM). Compounds 5b (IC50?=?13.96?μM) and 6b (IC50?=?13.96?μM) showed significant antioxidant activity. After performing molecular docking study and analyzing overall binding modes it was found that the synthesized compounds had potential to inhibit L. donovani pteridine reductase 1 enzyme. In silico ADME and metabolic site prediction studies were also held out to set an effective lead candidate for the future antileishmanial and antibacterial drug discovery initiatives.
Pleuromutilin derivative with 1, 3, 4-oxadiazole side chain and preparation and application thereof
-
Paragraph 0055-0056; 0070; 0090; 0094; 0095; 0102, (2021/07/24)
The invention belongs to the field of medicinal chemistry, and particularly relates to a pleuromutilin derivative with a 1, 3, 4-oxadiazole side chain and preparation and application thereof The pleuromutilin derivative with the 1, 3, 4-oxadiazole side chain is a compound shown in a formula 2 or a pharmaceutically acceptable salt thereof, and a solvent compound, an enantiomer, a diastereoisomer and a tautomer of the compound shown in the formula 2 or the pharmaceutically acceptable salt thereof or a mixture of the solvent compound, the enantiomer, the diastereoisomer and the tautomer in any proportion, including a racemic mixture. The pleuromutilin derivative has good antibacterial activity, is especially suitable for being used as a novel antibacterial agent for systemic system infection of animals or human beings, and has good water solubility.
Design, synthesis and antitrypanosomal activity of heteroaryl-based 1,2,4-triazole and 1,3,4-oxadiazole derivatives
Abdel-Aziz, Mohamed,Gouda, Ahmed M.,Marzouk, Adel A.,Radwan, Mohamed M.,Shaykoon, Montaser Sh.,Soltan, Osama M.,Wanas, Amira S.,Youssif, Bahaa G. M.
, (2020/05/22)
Two series of novel 1,2,4-triazol-3-yl-thioacetamide 3a-b and 4a-b and 5-pyrazin-2-yl-3H-[1,3,4]oxadiazole-2-thiones 9a-h were designed and synthesized. The compounds prepared have been identified using 1H NMR, 13C NMR and elemental analyses. The synthesized compounds 3a, 3b, 4a, 4b, 9a, 9b, 9d-e and 9f have been evaluated with α-difluoromethylornithine (DFMO) as a control drug for their in vitro antitrypanosomal activity against Trypanosoma brucei. Results showed that 3b was the most active compound in general and also more potent than control DFMO. 3b was 8 folds more potent than the reference with IC50 of 0.79 μM and IC90 of 1.35 μM, respectively compared to DFMO (IC50 = 6.10 μM and IC90 of 8.66 μM). The tested compounds showed moderate cytotoxicity with selectivity indices ranging from 12 (9d) to 102 (3b) against L6 cells. Docking study was performed into ten of T. brucei enzymes which have been identified as potential/valid targets for most of the antitrypanosomal agents. The results of the docking study revealed high binding scores toward many of the selected enzymes. A good correlation was observed only between log (IC50) of antitrypanosomal activity of the new compounds and their calculated Ki values against TryR enzyme (R2 = 0.726). Compound 3b, the most active as antitrypanosomal agents exhibited similar binding orientation and interaction to those of WP6 against TryR enzyme. However, in a next round of work, a complementary studies will be carried out to clarify the mechanism of action of these compounds.
