Dataset Information

Evaluation of Triazole and Isoxazole Derivatives as Potential Anti-infective Agents.

ABSTRACT: A series of isoxazole and triazole derivatives, with interesting bioactive scaffolds, were examined for their in vitro antibacterial, antifungal, and antiprotozoal activities. These compounds exhibited antitrypanosomal activity comparable to difluoromethylornithine (DMFO), a drug used in the treatment of human African trypanosomiasis. Isoxazole analogues 1, 3 and 4, and triazole derivatives 16, 17, 28, 37, 40 and 42 showed the highest antitrypanosomal activity with IC50 values of 17.89, 1.82, 10.38, 10.26, 11.77, 9.29, 3.93, 2.11, and 0.93 ?M, respectively. Compounds 40 and 42 showed the most potent activity against Leishmania donovani amastigotes with IC50 values of 18.28 and 10.54 ?M, respectively. Compound 42 showed the most potent activity against Leishmania donovani macrophage internalized amastigotes with an IC50 value of 8.32 ?M. Conjugate triazoles 40-43 displayed potential antimalarial activity against chloroquine-resistant W2 and chloroquine sensitive D6 Plasmodium falciparum strains (IC50 value range from 0.58 to 8.36 ?M). Compound 37 showed antibacterial activity against Staphylococcus aureus, MRSA and Mycobacterium intracellulare with IC50 values of 15.53, 14.22 and 47.45 ?M, respectively. None of the compounds exhibited antifungal activity.

SUBMITTER: Tarawneh AH

PROVIDER: S-EPMC6203334 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evaluation of Triazole and Isoxazole Derivatives as Potential Anti-infective Agents.

Tarawneh Amer H AH Al-Momani Lo Ay A LAA León Francisco F Jain Surenda K SK Gadetskaya Anastassiya V AV Abu-Orabi Sultan T ST Tekwani Babu L BL Cutler Stephen J SJ

Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents 20180227 4

A series of isoxazole and triazole derivatives, with interesting bioactive scaffolds, were examined for their in vitro antibacterial, antifungal, and antiprotozoal activities. These compounds exhibited antitrypanosomal activity comparable to difluoromethylornithine (DMFO), a drug used in the treatment of human African trypanosomiasis. Isoxazole analogues 1, 3 and 4, and triazole derivatives 16, 17, 28, 37, 40 and 42 showed the ...[more]

PMID: 30374214

Similar Datasets

Project description:BackgroundIsoxazole is an important pharmacophore in medicinal chemistry with a wide range of pharmacological activities. The present study deals with the synthesis and evaluation of antinociceptive potential of nine novel 3-substituted-isoxazole-4-carboxamide derivatives.SynthesisIn the first step, respective oxime was prepared and further treated with ethylacetoacetate and anhydrous zinc chloride followed by hydrolysis of ester to furnish 3-substituted isoxazole-4-carboxylic acid. The respective carboxylic acids were converted to acid chlorides and condensed with aromatic amines to get the target carboxamide derivatives (A1-A5 and B1-B5). These compounds were characterized by FTIR, 1HNMR, 13CNMR and elemental analysis data and screened for their analgesic activity using acetic acid-induced writhing assay and hot plat test in mice and compared with the standard centrally acting analgesic, tramadol.ResultsAll the synthesized carboxamide derivatives showed low to moderate analgesic activity. Among the synthesized derivatives B2 having methoxy (OCH3) showed high analgesic activity as compared to tramadol both in acetic acid-induced writhing assay and hot plate assay at dose of 6 mg/kg. To examine the involvement of opioidergic mechanism in the mediation of analgesic effects of isoxazole derivatives animals were further treated with non-selective opioid analgesic, naloxone (0.5 mg/kg). The results showed that compounds A3 and B2 follow a non-opioid receptor pathway in the mediation of analgesic effects. Synthesized compounds A3 and B2 were docked against non-opioid receptors COX-1 (3N8X), COX-2 (1PXX) and human capsaicin receptor (HCR, 3J9J) to analyze their binding interactions. They showed binding energies in the range of - 7.5 to - 9.7 kcal/mol.ConclusionsThe results indicated that isoxazole carboxamide derivatives possess moderate analgesic potential especially compounds A3 and B2 can be considered as lead molecules and explored further for pain management with fewer side effects.

Dataset Information

Evaluation of Triazole and Isoxazole Derivatives as Potential Anti-infective Agents.

Publications

Evaluation of Triazole and Isoxazole Derivatives as Potential Anti-infective Agents.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets