ABSTRACT
Toxicity in drug includes target toxicity, immune hypersensitivity and off target toxicity. Recently, advances in nanotechnology in the areas of drug delivery have help reduce toxicity and enhance drug solubility and deliver drugs to target sites more efficiently. In this study, we present a novel heteroatom functionalized quantum dot (QD-NBC and QD-NBS) as an effective drug delivery system for isoniazid. The said QD has been computationally modeled to assess its effectiveness in delivering isoniazid to desired target. Density functional theory (DFT) calculations were performed on the QD at the B3LYP/6-311+G(d, p) level to assess its stability through the natural bond orbital (NBO) calculations, and frontier molecular orbital (FMO) before and after interaction with isoniazid drug to understand any change in molecular behavior of the surface. Appropriate intermolecular interactions between the QD and the drug were computed through the Quantum theory of atoms in molecules (QTAIM) and Non-covalent interaction to assess the various binding mechanism and possible interactions resulting to the effective delivery of the drug target. To understand and accurately appraise the binding energy of adsorption, DFT calculations were performed with different functionals (B3LYP, CAM-B3LYP, PBEPBE, GD3BJ & WB97XD/6-311+G (d, p)). The results from DFT calculations point the functionalized QDs to be stable with appreciable energy gap suitable for delivery purposes. The adsorption energy of the drug target with the QD is in the range of -24.73 to 33.75 kcal/mol which indicates substantial interaction of the drug with the QD surface. This absorption energy is comparable with several reported literature and thus prompt the suitability of the surface for isoniazid delivery.
ABSTRACT
The problems associated with antibacterial drug discovery have kept the model of antibacterial drug to an extraordinary low level. Humans carry millions of bacteria; some species of bacteria can cause infectious disease, while some are pathogenic. Infectious bacteria which can reproduce quickly in the body can cause diseases such as tuberculosis, cholera, pneumonia, and typhoid, thus arises an urgent need to develop new drugs. Herein, 2-{[(2-hydroxyphenyl)methylidene]amino}nicotinic acid was synthesized from the condensation of o-phenylenediamine and 5-nitrosalicaldehyde followed by detailed characterization by ultraviolet-visible spectroscopy, vibrational studies FT-IR, nuclear magnetic resonance (1H-NMR, 13C-NMR), and gas chromatography coupled with mass spectroscopy (GC-MS). The complex synthesized was screened against selected microbes in order to establish their potential antimicrobial activity using selected known drugs as reference. From the results obtained, the Schiff base exhibited antimicrobial activity against all the tested microorganisms except Candida albicans isolate, which exhibited zero diameter zone of inhibition. The theoretical investigations of the synthesized compounds were computed using density functional theory (DFT) at the B3LYP/6-311 + + G(d, p) level of theory and in silico molecular docking simulation. By comparing binding affinity of the studied compound and the standard drug (ampicillin), the studied compound docked against bacterial protein showed a high binding affinity for E. coli 6.6 kcal/mol and makes it effective as an antibacterial agent for E. coli.
