Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8551980 | Regulatory Toxicology and Pharmacology | 2017 | 10 Pages |
Abstract
In spite of unprecedented advances in modern systems of medicine, there is necessity for exploration of traditional plant based secondary metabolites or their semisynthetic derivatives which may results in better therapeutic activity, low toxicity and favourable pharmacokinetics. In this context, computational model based predictions aid medicinal chemists in rational development of new chemical entity having unfavourable pharmacokinetic properties which is a major hurdle for its further development as a drug molecule. Para-coumaric acid (p-CA) and its derivatives found to be have promising antiinflammatory and analgesic activity. IS01957, a p-CA derivative has been identified as dual acting molecule against inflammation and nociception. Therefore, objective of the present study was to investigate pharmacokinetics, efficacy and safety profile based on in-silico, in-vitro and in-vivo model to assess drug likeliness. In the present study, it has excellent pharmacological action in different animal models for inflammation and nociception. Virtual pharmacokinetics related properties of IS01957 have resemblance between envision and experimentation with a few deviations. It has also acceptable safety pharmacological profile in various animal models for central nervous system (CNS), gastro intestinal tract (GIT)/digestive system and cardiovascular system (CVS). Finally, further development of IS01957 is required based on its attractive preclinical profiles.
Keywords
SGFtime to reach maximum plasma concentrationTNFRh123AUC0-∞AUC0-tRLMP-gptmaxSIFp-CAPAMPAGITNADPHADMECmaxDBPLPSPBSCVSSBPLC-MS/MSP-glycoproteint1/2enzyme linked immunosorbent assayinflammationstandard deviationinterferonIFNInterleukinesclearanceELISAParallel artificial membrane permeability assayabsorption, distribution, metabolism and excretionVolume of distributionmaximum plasma concentrationstandard error of meanSafety pharmacologyCNSGastrointestinal tractrapid equilibrium dialysisRhodamine 123REDcentral nervous systemCardiovascular systemSimulated intestinal fluidsimulated gastric fluidnociceptionPharmacokineticstumor necrosis factordiastolic blood pressuresystolic blood pressureSEMRat liver microsomesPermeabilitynicotinamide adenine dinucleotide phosphatePentobarbital sodiumliquid chromatography tandem mass spectrometryChlorpromazine hydrochloride
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Authors
Anjna Sharma, Asmita Magotra, Ashish Dogra, Santosh Kumar Rath, Sheikh Rayees, Priya Wazir, Sadhana Sharma, Payare Lal Sangwan, Surjeet Singh, Gurdarshan Singh, Utpal Nandi,