In silico evaluation of antipsychotic potential of phytoconstituents from Aframomum melegueta and Piper guineense
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Abstract
Background: Antipsychotic drugs are crucial for treating conditions like schizophrenia and bipolar disorder. However, many existing treatments are inadequate in managing cognitive impairments and negative symptoms, highlighting the need for alternative therapeutic options. This research aims at investigating the antipsychotic potential of bioactive compounds from Aframomum melegueta and Piper guineense through computational methods,
Methods: Phytochemicals of Aframomum melegueta and Piper guineense were obtained from PubChem in SDF format and docked against dopamine D2 (PDB ID: 7DFP) and serotonin 5-HT2A receptors (PDB ID: 7VOE) using Maestro version 12.8. Their binding affinities were compared with those of established antipsychotic drugs. Additionally, pharmacokinetic and toxicity characteristics were predicted using ADMET analysis.
Results: Compounds from both plants demonstrated strong binding affinity, particularly towards the dopamine D2 receptor, with several outperforming standard antipsychotics with CID 11000257 (–7.921 kcal/mol), CID 442879 (–8.334 kcal/mol), and CID 90472536 (–7.718 kcal/mol) exhibited serotonin receptor affinities comparable to reference drugs. CID 6989 (–6.381 kcal/mol), CID 615800 (–5.712 kcal/mol), and CID 6987 (–5.704 kcal/mol) also showed favourable dopamine receptor binding, similar to olanzapine (CID 135398745; serotonin: –8.802, dopamine: –6.372 kcal/mol) and risperidone (CID 5073; serotonin: –9.389, dopamine: –5.655 kcal/mol). ADMET evaluations indicated favourable absorption, distribution, metabolism, excretion, and toxicity profiles for most compounds analyzed
Conclusion: Piper guineense and Aframomum melegueta show potential as sources of novel antipsychotic agents. Further laboratory and preclinical studies, including molecular dynamics simulations, are warranted to confirm their therapeutic promise and advance their development into safer, more effective antipsychotic medications.
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