In Silico Evaluation of Biopharmaceutical Properties of Chloramphenicol Derivatives and their Iron Complexes

Author(s): Kananda Masonga Michel, Lumbwe Kitenge Edouard, Kayembe Kazadi Oscar, Mbayo Kitambala Marsi, Kalonda Mutombo Emery

Context and objectives The use of chloramphenicol (CAM) has been reduced due to the side effects associated with its use (Bone marrow depression, neurotoxicity) and the increase in resistance to CAM that some microbes develop. To overcome these difficulties, two CAM derivatives, L1 and L2, and their respective iron complexes were synthesized to evaluate in silico their biopharmaceutical properties.

Methodology Chloramphenicol, acetaminophen, and acetylsalicylic acid were purified from commercial pharmaceuticals. Synthesized compounds were characterized by staining tests and by UV-visible spectrophotometry. These were subjected to specialized bioinformatics tools such as PreADMET, and PkCSM, which allowed in silico prediction of ADMET properties and the Molinspiration tool was used to determine bioactivity scores of the synthesized products.

Results The substrate (CAM), as well as the basic reagents (AAP and AASC) were purified from commercial pharmaceuticals. The CAM derivatives (L1 and L2) and also their iron complexes (C1, C2, and C3) were synthesized and showed maximum absorbance at 335 nm for CAM, 325 nm for L1, 395 nm for L2, at 330 nm for C1, at 325 nm for C2, and at 335 nm for C3. The in silico simulations performed with the above-mentioned tools showed that all the ligands (CAM, L1, and L2) present good similarities with the drugs, a good bioavailability because they were compliant with the Lipinski rule. The complexes, although bioavailable, did not conform to Lipinski's rule. CAM showed efficacy in enzymatic inhibition. However, L1 and L2 ligands perform better in ion channel modulation, kinase, and protease inhibition. This suggests that the ligands have better therapeutic performance and may well address several clinical needs. The C3 complex was the compound that showed better bioavailabi