Long-term response to aminopyridines in a cohort of patients with ataxia associated with downbeat nystagmus due to the FGF14 GAA expansion.

Purpose: To propose a specific mode of action for the activity of the crude aqueous extract of Hippocratea welwitchii Oliv (Celastraceae) roots using specific models. Methods: The extract was evaluated for anticonvulsant activity using picrotoxin, 4-amino pyridine, N-methyl-D-aspartate (NMDA) and the effects of flumazenil on the extract on seizures caused by pentylenetetrazole (PTZ) in adult Swiss mice of either sex, locally bred, and weighing 20 ± 2 g at doses of 125, 250, and 500 mg/kg. Five groups of ten mice each were used for all tests. Extracts were given orally to all mice, while the convulsing agents were administered intraperitoneally after administration of the extract. Results: The extract at 125 and 250 mg/kg provided 100 and 80 % protection against mortality, respectively, while at a dose of 250 mg/kg, it afforded 60 % protection against NMDA-induced clonic spasm; this suggests the involvement of glutamatergic neurotransmission in its anticonvulsant activity. The extract did not produce any protection against death in the picrotoxin test, but it was able to prolong the time of death (14.72 ± 1.10) and onset of seizure (11.78 ± 1.21) at 125 mg/kg dose of the extract in the treated mice. Quite notably, the 500 mg/kg dose of the extract delayed seizure onset (16.49 ± 0.33) and time of death (18.36 ± 1.88) of the treated mice in 4-Aminopyridine induced convulsions. Conclusion: The aqueous crude extract of Hippocratea welwitchii exhibits promising antiepileptic potential, which can be further harnessed through more thorough biological analyses and additional research on the chemical description of the anticonvulsant active principles and definite mechanism of anticonvulsant action.

This study presents a novel approach for producing luminescent carbon quantum dots (CQDs) at room temperature (RT) utilizing hydroquinone and monosodium glutamate (MSG) as precursors through a simple reaction with no energy consumption. The produced RT-CQDs have a tiny diameter of 3.6 nm and a high quantum yield of 38.05%. Many spectroscopic and microscopic techniques, including HRTEM, zeta potential, EDX, FT-IR, UV/Visible, and fluorescence spectroscopy were utilized to characterize the produced RT-CQDs. After excitation at 290 nm, the RT-CQDs showed a high emission at 327 nm. The produced RT-CQDs' fluorescence signal was quantitatively decreased by dalfampridine (DFP), enabling their use as a sensitive fluorescent nanosensor to measure DFP in different matrices without the need for any pre-derivatization steps or a large volume of organic solvents, for the first time. The developed method showed a correlation coefficient of 0.9998, wide linearity range of 0.02–14.0 µg mL−1, and a detection limit of 0.005 µg mL−1, indicating the method's exceptional sensitivity. The proposed method was effectively used to determine DFP in tablets and human plasma samples, with low% RSD and high% recoveries. Moreover, the DFP tablets' content uniformity testing was carried out in compliance with USP criteria. Furthermore, the newly published greenness, blueness, and violetness assessment tools proved the low environmental effect, excellent practicality, good analytical performance, and novelty of the proposed DFP sensing approach. The developed method was fully validated according to ICH guidelines. The production of CQDs with superior qualities at room temperature under mild conditions opens the door for further developments in CQD room temperature synthesis and provides an effective substitute for conventional synthesis methods.

Synthesis of functionalized magnetic Fe3O4 nanocomposites for efficient capture and recover Ag(I) from e-waste.

Novel azo ligand namely (E)-1,3,7-trimethyl-8-(pyridin-3-yldiazenyl)-3,7-dihydro-1H-purine-2,6-dione (MPPD) derived from 3-aminopyridine and caffeine and its palladium complex were synthesized and characterized by different techniques such as 1H-NMR, infrared, UV-Vis spectroscopies and elemental analysis. The infrared spectra indicated that the ligand is bidentate. 1H-NMR spectra showed the ligand structure and the symmetrical nature of the ligands bound to the palladium ion in the complex. UV-Vis spectra suggested a square planer environment for the complex of palladium and the molar conductivity indicated an ionic nature equal to 1:2 for the palladium(II) complex. The synthesized compounds showed high ability and efficacy to determine the latent fingerprint and deep learning technique enhanced the images of latent fingerprint. KEY WORDS: Fingerprint, Palladium, Azo, Caffeine, Green chemistry, Deep learning Bull. Chem. Soc. Ethiop. 2025, 39(11), 2173-2184. DOI: https://dx.doi.org/10.4314/bcse.v39i11.7

Tetrazole and its derivatives are one of the most common five-membered heterocyclic compounds that receive great attention from researchers. Their importance is due to their multiple applications in various fields, such as industrial, medical, and agricultural applications. The aim of the current study is to obtain a new nucleus for the active compound 4- aminoantipyrene with an active group, which is the formyl group, then link it with different amines to form compounds (Schiff bases) that contain the active group ( C=N ) azomethine and convert them to the heterogeneous pentacyclic system called tetrazoles which is expected to have promising biological effectiveness. In this study, (E)-3-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) diazenyl)-4-hydroxybenzaldehyde (AZ1) was prepared by the reaction of 4-aminoantipyrine Diaz onium salts and 4- hydroxybenzaldehyde under base conditions. Schiff bases (2-6) were synthesized by the condensation of compound (1) and aromatic amines such as (4-aminoaniline, , 3-nitroaniline, 4-amino pyridine, 4-aminoantipyrin and 2,4-dinitroaniline). A novel of five member-rings of Tetrazoles (A7-A11) were created through the interaction of Schiff bases and sodium azide. IR as well as NMR spectrum investigations validated the structure of the resulted compounds example (A10 and A5) compounds A novel of five member-rings of Tetrazoles (A7-A11) were created through the interaction of Schiff bases and sodium azide. IR as well as NMR spectrum investigations validated the structure of the resulted compounds example (A10 and A5) compounds

Cyclodextrins (CDs) have emerged as a promising strategy for the targeted drug delivery process. Herein, the potential of β-cyclodextrin (β-CD) as a drug delivery system for the Ampyra (AMP) drug was extensively investigated. By means of the molecular dynamics (MD) simulation technique, the inclusion process of AMP with β-CD was first examined and consequently subjected to clustering analysis. Upon the obtained five configurations (A↔E) of AMP⋯β-CD complex, extensive density functional theory (DFT) calculations were executed. The favorability of the quested encapsulation process was affirmed by negative adsorption and interaction energies of the selected configurations A↔E affirmed the occurrence of the quested encapsulation process. In particular, configuration A is more energetically preferred compared to other analogs. The insights from SAPT analysis verified the dominant role of electrostatic and dispersion forces in the interactions within the studied configurations A↔E. From QTAIM and NCI analyses, the occurrence and nature of intermolecular interactions within the studied configurations A↔E were illustrated. As per the electronic analysis, the effect of the AMP encapsulation process on the electronic features of β-CD was emphasized. The enhancing impact of the aqueous medium on the studied configurations A↔E was verified by negative adsorption and solvation energies. Moreover, the calculated recovery time values pinpointed the separation potential of AMP from β-CD at the target cell. Overall, the obtained outcomes provided insights into the potential application of β-CD as a drug delivery system, particularly for AMP drug.

Nanoscale-assisted drug delivery systems give a platform to alter elementary properties associated with drug particles to limit their adverse effects. In this regard, deep benzimidazolone cavitand-based dimeric nanocapsule, which can act as good host for small guest molecules, is considered to be used as drug delivery vehicle. In the current study, we report the benzimidazolone cavitand-based nanocapsules as drug delivery systems for the drugs, i.e. ampyra (AM) and merceptopurine (MP) at M06−2x/6−31G(d,p) level of theory. AM and MP drugs interact with the nanocapsule with the interaction energies of −26.02 kcal mol−1 and −24.01 kcal mol−1, respectively. The results of quantum theory of atoms in molecules (QTAIM) and non-covalent index (NCI) analyses divulge that both the drug molecules are stabilized inside nanocapsule via the hydrogen bonding and van der Waals interactions. The transfer of charge is confirmed through electron density difference (EDD) analyses. Moreover, in the case of MP@cap slightly higher transfer of charge (natural bond orbital; NBO) is observed as compared with AM@cap. Furthermore, frontier molecular orbital (FMO) analyses show the higher energy gap reduction in the case of MP@cap as compared with nanocapsule. The FMO results are consistent with the results of interaction energies, NBO and EDD analyses. Additionally, we have employed ab initio molecular dynamics (AIMD) analysis to find the dynamical stability of drug delivery system after drug loading. Molecular docking has been performed for binding kinetics or the enzymatic interactions of the selected drugs. And, pH effect is studied for understanding the off-loading mechanism of the drugs, which clearly shows the decrease in Eint values pointing towards easier offloading. The analyses of values of dipole moment show that nanocapsule will carry MP drug more efficiently to the target site as compared with AM drug molecule. Overall, the results divulge that the benzimidazolone cavitand-based nanocapsule acts as better carrier for an anti-cancer drug molecule as compared with the other drugs.

We demonstrated the design and photophysical properties of a dual-state emissive π-conjugated dipyridyl-dipyrroethene chromophore (6) synthesized via selective diformylation of (E)-dipyrroethene followed by condensation with 2-amino pyridine. The rational molecular design, incorporating both hydrogen bonding and π···π interactions, leads to a unique supramolecular architecture in the solid state, and the system exhibits aggregation-induced emission properties. We further extend the applicability of chromophore 6 for the selective detection of serum albumin.

Aminopyridines (APs) enhance Purkinje cell excitability and are effective for several cerebellar and ocular motor syndromes, including downbeat nystagmus. Their use in anti–glutamic acid decarboxylase (GAD) cerebellar ataxia has not previously been described. A 69-year-old woman with confirmed anti-GAD cerebellar ataxia underwent clinical and videonystagmography (VNG) assessments at baseline, Day 7, and Day 30 after start of fampridine 20 mg/day. Baseline VNG showed pronounced downbeat nystagmus and frequent square-wave jerks. By Day 7, downbeat nystagmus had fully resolved with a marked reduction in square-wave jerks, accompanied by improvement in oscillopsia and diplopia. Findings remained stable at Day 30. SARA scores remained unchanged, with persistent gait, stance, and other cerebellar motor deficits. Fampridine was associated with rapid and sustained improvement in oculomotor dysfunction in this patient with anti-GAD cerebellar ataxia. APs may offer adjunctive symptomatic benefit in selected individuals with visually disabling downbeat nystagmus. Controlled studies are needed to confirm these observations.

We have developed an efficient and straightforward synthetic route to obtain naphthoquinone-fused pyrrole derivatives (up to 93% yield) via an intramolecular cyclization of 2-(arylethynyl)naphthalene-1,4-dione derivatives with NH4OAc in methanol at ambient temperature. Furthermore, imidazopyridinedione derivatives were synthesized via coupling between 2-bromonaphthalene-1,4-dione and 2-amino pyridine through condensation and rearrangement under neat conditions in the presence of a catalytic amount of AcOH. A series of functionalized pyrrolonaphthoquinone and imidazopyridinedione derivatives were synthesized in high yields. Additionally, one of the synthesized pyrrolonaphthoquinones was selected as the model substrate for evaluating cytotoxicity and antimicrobial activity against both Gram-positive and Gram-negative biofilm bacteria.

Chronic myeloid leukaemia (CML) is primarily treated using imatinib mesylate, a tyrosine kinase inhibitor (TKI) targeting the BCR::ABL1 oncoprotein. However, the development of drug resistance and adverse side effects necessitate the exploration of alternative therapeutic agents. This study presents the synthesis and characterization of a novel imatinib analogue, 3-chloro-N-(2-methyl-5-((4-(pyridin-2-yl)pyrimidin-2-yl)amino)phenyl)benzamide (PAPP1). The compound’s structure was elucidated using X-ray crystallography and spectroscopic techniques, including NMR, infrared and UV–visible. Crystallographic analysis reveals that PAPP1 consists of a phenyl–amino–pyridine–pyrimidine (PAPP) scaffold with substituted aromatic rings forming a nearly coplanar geometry. Additionally, supramolecular interactions in the crystal are mediated by hydrogen bonds and dispersion forces, forming dimers and layered structures. Molecular docking studies demonstrate strong binding affinity to the ABL1 enzyme, with PAPP1 showing comparable binding energy to imatinib, indicating its potential as a lead compound for further development. Computational studies, including molecular electrostatic potential and vibrational analysis, provide further support for the structural stability and bioactivity of PAPP1. These findings suggest that PAPP could be a promising scaffold for future CML drug design, offering a potential alternative to existing TKIs, and PAPP1 is a promising lead susceptible to optimization.

Individuals with downbeat nystagmus (DBN) syndrome present with DBN, dizziness, blurred vision, and unsteady gait. Pharmacological intervention with 4-aminopyridine (4-AP) may be effective in improving oculomotor function, but there is minimal evidence to date that it improves gait. This suggests the possible benefit of combining pharmacotherapy with physical therapy to maximize outcomes. This case report documents improvements in gait and balance after physical therapy and aminopyridine (AP) in an individual with DBN syndrome. The patient was a 70-year-old man with a 4-year history of worsening dizziness and imbalance, diagnosed with DBN syndrome. He demonstrated impaired oculomotor function, dizziness, and imbalance, which resulted in falls and limited community ambulation. The patient completed a customized, tapered course of physical therapy over 6months. Outcome measures included the 10-meter walk test, the Timed Up and Go (TUG), the Dynamic Gait Index (DGI), and the modified clinical test of sensory integration and balance. Improvements exceeding minimal detectable change were demonstrated on the TUG and the DGI. Gait speed on the 10-meter walk test did not change significantly, but the patient was able to use a cane to ambulate in the community and reported no further falls. Controlled studies are needed to explore the potential for AP to augment physical therapy in people with DBN syndrome. Physical therapists are encouraged to communicate with referring medical providers about the use of AP as pharmacotherapy along with physical therapy for individuals with DBN syndrome.

Innovative modification of cyclodextrin metal-organic frameworks for enhanced adsorption in wastewater treatment

Neglected tropical diseases (NTDs) pose a major threat in tropical zones for impoverished populations. Difficulty of access, adverse effects or low efficacy limit the use of current therapeutic options. Therefore, development of new drugs against NTDs is a necessity. Compounds containing an aminopyridine (AP) moiety are of great interest for the design of new anti-NTD drugs due to their intrinsic properties compared with their closest chemical structures. Currently, over 40 compounds with an AP moiety are on the market, but none is used against NTDs despite active research on APs. The aim of this review is to present the medicinal chemistry work carried out with these scaffolds, against protozoan NTDs: Trypanosoma cruzi, Trypanosoma brucei or Leishmania spp.

This research investigated the anticonvulsant effect of the crude extract and fractions of Solanum americanum’s (S.a.) leaves on seizures induced by pentylenetetrazole (PTZ) and 4- amino pyridinein albino rats to authenticate the use of the leaves in the treatment of epilepsy in South -Eastern Nigeria. The leaves of S.a were extracted with methanol and fractionated using n-hexane, ethyl acetate and methanol. The parameters observed were onset of convulsions in minutes, duration of clonic phase in minutes, percentage protection from seizures and mortality. The anticonvulsant tests were carried out using 60 (sixty) white albino rats (weighing 80-136 g) of both sexes, varying concentrations of both methanol extracts and fractions (12.5, 25.0, 50.0, 100 and 200 mg/kg b.w.) were administered to the rats after which convulsion were induced in the rats using 9.0 mg/kg of PTZ and 1.5 mg/kg 4-amino pyridine on different groups (35 and 25) of rats respectively. The results of the various groups were compared with the control group and significance was analyzed by one-way ANOVA. The acute toxicity test was conducted at a dose of 3000 mg/kg. At a peak dose of 200 mg/kg methanol crude extract, hexane and methanol fraction in PTZ model protected the animals from seizure at 89.30%, 100%, 100% but gave 80%, 80% and 60% protection from mortality respectively. Hexane fraction (12.5, 25, 50, 100 and 200 mg/kg) protected the rats against mortality at 20%, 40%, 60%, 60% and 80% respectively, while no anticonvulsant activities were detected in ethyl acetate fraction. Differences among the means and standard deviation was statistically significant at P < 0.05.The acute toxicity test showed that the leaf of S.a. is non-toxic. The result obtained substantiated the use of the leaf of Solanum americanum ethnobotanically as anticonvulsant.

Abstract Two organic cocrystals, one ( 1 ) based on benzene 1,3,5 tricarboxylic acid (TMA) plus 4‐amino pyridine and another ( 2 ) based on benzene 1,3,5 tricarboxylic acid (TMA) plus urea is reported. Cocrystals 1 and 2 are fully characterized by single crystal X ray diffraction, NMR and IR spectroscopy. The single crystal X ray diffraction shows the intermolecular H‐bonding interaction between components of the pairs TMA‐TMA as well as TMA‐4 amino pyridine and TMA‐Urea molecules. The conductivity studies for the cocrystal 1 shows semiconducting behavior whereas cocrystal 2 remain as insulator under the same experimental condition. Computational studies with theoretically optimized structures as well as experimental X‐ray structures of both the cocrystals reveal the origin of conductivity as the H‐atom coupled charge transfer through the intermolecular H‐bonding between TMA and 4‐amino pyridine in cocrystal 1 .

Abstract To study the antikinetoplastid structure–activity relationships in a 3-nitroimidazo[1,2-a]pyridine series, we explored the substitution of positions 5 and 7 of the scaffold, developing nucleophilic aromatic substitution reactions and palladium-catalyzed Suzuki–Miyaura, Sonogashira, and Buchwald–Hartwig cross-coupling reactions that had never been reported at these positions in this series. In four steps from 2-amino(bromo)pyridines, 33 original compounds were obtained, allowing a better definition of the antiparasitic pharmacophore.

In this research, new azochalcone derivatives (6, 7) were synthesized by using three methods: the first one is diazotization - coupling method of different aromatic amines (sulfanilic acid, 2-aminopyridine) with chalcone (5), the second, aldol condensation method of azoaryl hydroxyacetophenone compounds with 4-dimethylamino benzaldehyde in presence of sodium hydroxide as a catalyst, the last one is method of aldol condensation of azoaryl hydroxyacetophenone compounds with 4-dimethylaminobenzaldehyde in presence of piperidine as an organic catalyst. The yield was the best by using the aldol condensation method with sodium hydroxide as a catalyst. New azoflavone derivatives (8, 9) with good yields (78-84 %) were also synthesized by performing cyclization reactions of azochalcone derivatives using iodine in dimethyl sulfoxide. The identity of the new compounds was determined using spectroscopic methods (FT-IR, 13C-NMR, 1H-NMR).

Effect of 2-amino pyridine inhibitor on the rehabilitation of chloride contaminated reinforced concrete with bidirectional electromigration method