Mohammed Faiz Arshad

Neurological disorders, including Down syndrome, Alzheimer’s disease, and autism spectrum disorders, involve intricate disruptions in brain function and development. DYRK1A (Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A) has become an essential target in these diseases because it helps neurons grow, differentiate, and change shape. Overexpression of DYRK1A is connected to problems with neurodevelopment, memory loss, and tauopathies, which makes it an essential target for therapy. Therefore, inhibiting the DYRK1A protein aids in maintaining the normal brain molecular mechanism. Herein, we have identified three major natural compounds, ZINC000043552589, ZINC000001562130, and ZINC000059779788, as potential inhibitory candidates. These compounds exhibited a strong binding affinity with the DYRK1A protein during virtual screening and molecular docking. During the virtual screening analysis, the binding scores of these compounds were more than -11.0 kcal/mol. Further, hydrogen and hydrophobic interactions strengthen their binding with the DYRK1A protein. The MD simulation analysis also confirmed the structural dynamic stability of the compounds. Moreover, the total free binding energy calculated via the MM/GBSA method was found to be -54.06 kcal/mol for ZINC000043552589, -39.01 kcal/mol for ZINC000001562130 and -50.26 kcal/mol for ZINC000059779788. These values further confirm the binding affinity strength of the compounds with the target protein. DFT analysis revealed distinct HOMO–LUMO energy gaps and orbital distributions across the compounds, highlighting their varied electronic characteristics and charge-transfer potentials. Network pharmacology analysis further highlighted multiple potential gene targets for the selected compounds, providing insights into their broader therapeutic implications. This analysis suggests these natural compounds may modulate additional pathways relevant to neurodevelopmental and neurodegenerative diseases.

For many decades, the thiazole moiety has been an important heterocycle in the world of chemistry. The thiazole ring consists of sulfur and nitrogen in such a fashion that the pi (π) electrons are free to move from one bond to other bonds rendering aromatic ring properties. On account of its aromaticity, the ring has many reactive positions where donor–acceptor, nucleophilic, oxidation reactions, etc., may take place. Molecules containing a thiazole ring, when entering physiological systems, behave unpredictably and reset the system differently. These molecules may activate/stop the biochemical pathways and enzymes or stimulate/block the receptors in the biological systems. Therefore, medicinal chemists have been focusing their efforts on thiazole-bearing compounds in order to develop novel therapeutic agents for a variety of pathological conditions. This review attempts to inform the readers on three major classes of thiazole-bearing molecules: Thiazoles as treatment drugs, thiazoles in clinical trials, and thiazoles in preclinical and developmental stages. A compilation of preclinical and developmental thiazole-bearing molecules is presented, focusing on their brief synthetic description and preclinical studies relating to structure-based activity analysis. The authors expect that the current review may succeed in drawing the attention of medicinal chemists to finding new leads, which may later be translated into new drugs.

Coronavirus disease 2019 (COVID-19) has become a major challenge affecting almost every corner of the world, with more than five million deaths worldwide. Despite several efforts, no drug or vaccine has shown the potential to check the ever-mutating SARS-COV-2. The emergence of novel variants is a major concern increasing the need for the discovery of novel therapeutics for the management of this pandemic. Out of several potential drug targets such as S protein, human ACE2, TMPRSS2 (transmembrane protease serine 2), 3CLpro, RdRp, and PLpro (papain-like protease), RNA-dependent RNA polymerase (RdRP) is a vital enzyme for viral RNA replication in the mammalian host cell and is one of the legitimate targets for the development of therapeutics against this disease. In this study, we have performed structure-based virtual screening to identify potential hit compounds against RdRp using molecular docking of a commercially available small molecule library of structurally diverse and drug-like molecules. Since non-optimal ADME properties create hurdles in the clinical development of drugs, we performed detailed in silico ADMET prediction to facilitate the selection of compounds for further studies. The results from the ADMET study indicated that most of the hit compounds had optimal properties. Moreover, to explore the conformational dynamics of protein–ligand interaction, we have performed an atomistic molecular dynamics simulation which indicated a stable interaction throughout the simulation period. We believe that the current findings may assist in the discovery of drug candidates against SARS-CoV-2.

A bunch of β-naphthalene incorporated thiazole-5-carboxamides/thiazole -5- ketones (7a-7o& 8a-8e) were prepared by reacting 4-methyl-2-(naphthalen-2-yl)thiazole-5-carbonyl chloride with appropriate amines. Structures of all the compounds were explained by elemental analysis, FT-IR, 1H NMR and mass spectral data. The compounds were evaluated for their anticonvulsant activity employing MES and chemoshock (scPTZ) seizure tests. Neurotoxicity was also assessed. Majority of these compounds exhibited significant activity against both animal models; however, compounds 7e, 7j, 7n and 8c displayed promising activity and could be considered as leads for further investigations.

The present study was designed to investigate the effects of the extract of green tea and/or ginger on some hematological and immunobiochemical profiles in alloxan-induced diabetic rabbits. The results revealed that treatment of diabetic animals with extract of green tea and/or ginger elevated the decreased HDL-c and LDL-c but significantly decreased triglycerides, the elevated glucose and GOT concentrations. The result also displayed a non-significant increase in the levels of CRP and fibrinogen. The experiment also revealed that the elevated MDA and GSH level fell down to the normal control group. The result also showed that after green tea and/or ginger extract treatment, the lowered RBC, WBC counts, PCV, percentage of neutrophils were increased and the elevated MCV, MCH, and MCHC of diabetic rabbits were decreased to normal levels. Thus, the overall results may indicate that green tea and/or ginger extracts have a significant hypoglycemic effect in diabetic rabbits. In addition, the extracts may be capable of improving hyperlipidemia, the impaired kidney function and hemogram in alloxan-induced diabetic rabbits.

Quinoline and its analogues have been known to possess diverse pharmacological activities. In the last three decades 2-chloro-8-methyl-3-formylquinoline has been utilized as building blocks for the development of various quinolines fused heteroaryl rings. In this article we report the complete spectral details of 2-chloro-8-methyl-3-formylquinoline. The techniques involved in the characterization of title compounds are various NMR experiments such as HSQC, COSY and HMBC. Molecular weight was determined by FAB-mass spectrometry. The powder XRD study revealed crystal behavior of the title compound.