Physicochemical, pharmacokinetic, efficacy and toxicity profiling of a potential nitrofuranyl methyl piperazine derivative IIIM-MCD-211 for oral tuberculosis therapy via in-silico –in-vitro–in-vivo approach

Publication date: February 2018 Source:Pulmonary Pharmacology & Therapeutics, Volume 48 Author(s): Asmita Magotra, Anjna Sharma, Samsher Singh, Probir Kumar Ojha, Sunil Kumar, Naveen Bokolia, Priya Wazir, Shweta Sharma, Inshad Ali Khan, Parvinder Pal Singh, Ram A. Vishwakarma, Gurdarshan Singh, Utpal Nandi Recent tuberculosis (TB) drug discovery programme involve continuous pursuit for new chemical entity (NCE) which can be not only effective against both susceptible and resistant strains of Mycobacterium tuberculosis (Mtb) but also safe and faster acting with the target, thereby shortening the prolonged TB treatments. We have identified a potential nitrofuranyl methyl piperazine derivative, IIIM-MCD-211 as new antitubercular agent with minimum inhibitory concentration (MIC) value of 0.0072 μM against H37Rv strain. Objective of the present study is to investigate physicochemical, pharmacokinetic, efficacy and toxicity profile using in-silico, in-vitro and in-vivo model in comprehensive manner to assess the likelihood of developing IIIM-MCD-211 as a clinical candidate. Results of computational prediction reveal that compound does not violate Lipinski's, Veber's and Jorgensen's rule linked with drug like properties and oral bioavailability. Experimentally, IIIM-MCD-211 exhibits excellent lipophilicity that is optimal for oral administration. IIIM-MCD-211 displays evidence of P-glycoprotein (P-gp) induction but no inhibition ability in rhodamine cell exc...
Source: Pulmonary Pharmacology and Therapeutics - Category: Respiratory Medicine Source Type: research