BIBLIOS

Document type
Journal articles

Document subtype
Full paper

Title
Lipophilicity assessment of some isoniazid derivatives active against Mycobacterium tuberculosis

Participants in the publication
M. Soledade C.S. Santos (Author)
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA
Dep. Química e Bioquímica
CQE
Ana Marta Matos (Author)
CQE
Marina Reis (Author)
Filomena Martins (Author)
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA
Dep. Química e Bioquímica
CQE

Summary
Micelle-water partition coefficients, log Kp(NaDS/w), and octanol-water partition coefficients, log Po/w, for 9 isoniazid derivatives, previously assessed as active against Mycobacterium tuberculosis, were determined using derivative spectrophotometry and the shake flask method in buffer systems at adequate pH values and ionic strength (0.1M). \\\\nMost of the compounds conform to a linear dependence between log Kp(NaDS/w) and log Po/w demonstrating that lipophilicity is predominantly determined by hydrophobic, non-specific, interactions. A regression slope, lower than 1 (0.81), signals partition of neutral compounds towards micellar media as less favorable than towards octanol. \\\\nThe 2 most hydrophobic compounds show negative deviations from the correlation line, which were reasoned in terms of size effects. Steric packing constraints in the micellar palisade, explain the decreased affinity of the bulkier compounds towards micellar media. This effect is partially compensated in the case of the N’-C10 INH derivative, due to a larger positive entropic contribution for the transfer process from the aqueous towards the micellar phase due to a “better fit” within the micellar hydrocarbon core. \\\\nTo the best of our knowledge, the systematic comparison of lipophilicity scales, sensitive to different molecular interactions, has never been used before, within a family of closely related compounds. The experimental data obtained provided relevant insights and foresee specific interactions of compound N’-C10 INH with biological membranes which support previous molecular dynamic simulations and bioactivity evaluation studies.


Institution
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA

Where published
Colloids and Surfaces A: Physicochemical and Engineering Aspects

Publication Identifiers
ISSN - 0927-7757

Publisher
Elsevier BV



Document Identifiers
DOI - https://doi.org/10.1016/j.colsurfa.2020.124820
URL - http://dx.doi.org/10.1016/j.colsurfa.2020.124820

Rankings
SCOPUS Q1 (2019) - 5.8 - Surfaces and Interfaces
SCIMAGO Q1 (2019) - 0.78 - Surfaces and Interfaces
Web Of Science Q2 (2019) - 3.990 - Chemistry, Physical

Keywords
Isoniazid derivatives Lipophilicity Octanol-water partition Micelle-water partition Hydrophobic interactions Stereochemical constraints