Drug Repurposing Using FDA Adverse Event Reporting System (FAERS) Database

Current Drug Targets, Journal Year: 2024, Volume and Issue: 25(7), P. 454 - 464

Published: April 3, 2024

Drug repurposing is an emerging approach to reassigning existing pre-approved therapies for new indications. The FDA Adverse Event Reporting System (FAERS) a large database of over 28 million adverse event reports submitted by medical providers, patients, and drug manufacturers provides extensive safety signal data. In this review, four common strategies using FAERS are described, including inverse detection single disease, drug-drug interactions that mitigate target ADE, identifying drug-ADE pairs with opposing gene perturbation signatures congruent signatures. purpose review provide overview these different approaches successful applications in the literature. With fast expansion reports, FAERS-based represents promising strategy discovering uses therapies.

Language: Английский

---

Design, synthesis, and biological evaluation of 1,2,4-oxadiazole-based derivatives as multitarget anti-Alzheimer agents

RSC Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 15(6), P. 2080 - 2097

Published: Jan. 1, 2024

A series of novel 1,2,4-oxadiazole-based derivatives were synthesized and evaluated for their potential anti-Alzheimer disease activity.

Language: Английский

---

Targeting SARS-CoV-2 nonstructural protein 3: Function, structure, inhibition, and perspective in drug discovery

Drug Discovery Today, Journal Year: 2023, Volume and Issue: 29(1), P. 103832 - 103832

Published: Nov. 16, 2023

Language: Английский

---

Investigating the Anticancer Activity of Novel 1,2,4-Oxadiazole-Linked 1,2,3-Triazole Moieties via EGFR/pI3K/mTOR Cascade Down-Regulation

Polycyclic aromatic compounds, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 20

Published: March 17, 2025

Language: Английский

---

New 1,2,4-oxadiazole derivatives as potential multifunctional agents for the treatment of Alzheimer’s disease: design, synthesis, and biological evaluation

BMC Chemistry, Journal Year: 2024, Volume and Issue: 18(1)

Published: July 13, 2024

Abstract A series of new 1,2,4-oxadiazole-based derivatives were synthesized and evaluated for their anti-AD potential. The results revealed that eleven compounds ( 1b , 2a-c 3b 4a-c 5a-c ) exhibited excellent inhibitory potential against AChE, with IC 50 values ranging from 0.00098 to 0.07920 µM. Their potency was 1.55 125.47 times higher than donepezil (IC = 0.12297 µM). In contrast, the newly oxadiazole in range 16.64 – 70.82 µM less selectivity towards BuChE when compared rivastigmine 5.88 Moreover, derivative 2c 463.85 µM) more potent antioxidant quercetin 491.23 Compounds 536.83 3c 582.44 comparable activity quercetin. Oxadiazole 140.02 4c 117.43 showed prominent MAO-B They biperiden 237.59 1a 3a 4b remarkable MAO-A potential, 47.25 129.7 1.1 3.03 methylene blue 143.6 Most provided significant protection induced HRBCs lysis, revealing nontoxic effect compounds, thus making them safe drug candidates. unveiled 2b 3b, 4a, 5a as multitarget agents. high AChE can be computationally explained by derivatives’ interactions active site. Compound good physicochemical properties. All these data suggest could considered a promising candidate future development.

Language: Английский

---

Thiol-promoted intermolecular cyclization to synthesize 1,2,4-oxadiazoles including tioxazafen under transition metal-free conditions

Organic & Biomolecular Chemistry, Journal Year: 2023, Volume and Issue: 21(27), P. 5616 - 5621

Published: Jan. 1, 2023

A simple and efficient one-pot intermolecular annulation reaction for the synthesis of 1,2,4-oxadiazoles from amidoximes benzyl thiols has been developed, in which act as not only reactants but also organo-catalysts. The control experiments proved that thiol substrates could facilitate dehydroaromatization step. High yield, functional group diversity transition metal-free, extra oxidant-free, mild conditions are important practical features. Moreover, this protocol provides an effective alternative method a commercially available broad-spectrum nematicide, tioxazafen.

Language: Английский

---

Syntheses, characterizations, and Hirshfeld analysis of Ag(I) and Cu(II) complexes: A novel potent Ag(I)‐based oxadiazole anticancer agent

Applied Organometallic Chemistry, Journal Year: 2023, Volume and Issue: 37(8)

Published: May 24, 2023

The Ag(I) and Cu(II) complexes of the ligand, 2,2′‐(1,2,4‐oxadiazole‐3,5‐diyl) dianiline, ( L ; 4 ) were synthesized characterized using different spectroscopic techniques. Their anticancer activities against three types cancer cell lines explored. [AgL (NO 3 )] n complex 5 has 1D polymeric structure whereas [CuL 2 ] 6 [CuLCl 7 are monomeric complexes. in is tetra‐coordinated AgN O coordination sphere where both NO ¯ bridging sites along polymer array. In , environments CuN Cl respectively. cases, oxadiazole ligand a tridentate chelate via two N‐atoms from amino groups one N‐atom moiety. Hirshfeld analysis revealed importance … H (23.5%), (24.8%), C (6.6%) non‐covalent interactions molecular packing . (40.7%), N (4.9%), (5.9%), (3.2%), (2.2%) contacts most important. Regarding safety on normal human fibroblasts Wi‐38, MTT assay for all metal especially exhibited higher profiles than free as well standard chemotherapeutic drug 5‐fluroruracil (5‐FU). cytotoxic – surpassed 5‐FU A549, Caco‐2, MDA‐MB231 lines. best activity (IC 50 = 0.074, 0.085, 0.533 μM, respectively) exhibiting pronounced selectivity index up to 44.3. Quantitative PCR BAX BCL‐2 their apoptotic induction mechanism showed that can repress main oncogene enhance expression proapoptotic gene BAX. Again, potent with 14.28 folds downregulation 4.86 upregulation.

Language: Английский

---

N-Arylamino-1,2,4-oxadiazol-5(4H)-ones: Synthesis, Luminescent, Antibacterial, and Antienteroviral Properties

Russian Journal of General Chemistry, Journal Year: 2024, Volume and Issue: 94(S1), P. S91 - S99

Published: Jan. 1, 2024

Language: Английский

---

Design, Synthesis, and In Vitro and In Silico Evaluation of 1,3,4‐Oxadiazoles as Anti‐Trypanosoma cruzi and Anti‐Leishmania mexicana Agents

ChemMedChem, Journal Year: 2024, Volume and Issue: 19(23)

Published: Aug. 13, 2024

Abstract A series of novel 4‐acetyl‐1,3,4‐oxadiazole derivatives was designed and synthesized for their biological evaluation in vitro against Trypanosoma cruzi ( T. ) Leishmania mexicana L. ). Additionally, all compounds were evaluated by molecular docking on the cruzain Tc Cz) cysteine protease B (CPB) Lm CPB) to know potential mechanism binding. Compound OX‐12 had better trypanocidal activity NINOA (IC 50 =10.5 μM) A1 =21.7 strains that reference drug benznidazole =30.3 μM 39.8 μM, respectively). OX‐2 best M379 =11.9 FCQEPS =34.0 glucantime >120 μM). All showed important interactions with residues active site Cz (Gly66, Trp26, Leu67, Ala138) CPB (Gly67, Asn62, Leu68, Ala140). Finally, dynamics simulations compound shown moderate stability from 40–115 ns an RMSD value 6.5 Å. Meanwhile, a minor complex 25–200 simulation (RMSD<9 Å). These results encourage develop more potent efficient leishmanicidal agents using 1,3,4‐oxadiazole scaffold.

Language: Английский

---

I₂-catalyzed tandem sp³ C–H oxidation and annulation of aryl methyl ketones with amidoximes for the synthesis of 5-aroyl-1,2,4-oxadiazoles

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: 22(36), P. 7478 - 7484

Published: Jan. 1, 2024

A metal-free, iodine-catalyzed protocol for the synthesis of biologically significant 5-aroyl 1,2,4-oxadiazole scaffolds has been developed using aryl methyl ketones and amidoximes.

Language: Английский

---