Discovery of pharmacological agents for triple-negative breast cancer (TNBC): molecular docking and molecular dynamic simulation studies on 5-lipoxygenase (5-LOX) and nuclear factor kappa B (NF-κB).

Global burden of breast cancer is expected to cross 26 million new cases by 2030. The term 'triple negative breast cancer' (TNBC) refers to lack of expression of hormone receptors (ER, PR and HER2). 5-Lipoxygenase (5-LOX) inhibition promotes breast cancer apoptosis, ferroptosis and inhibits metastases. Nuclear factor kappa B (NF-κB) activation induces cell survival in breast cancer through stimulation of angiogenesis. Therefore, inhibiting NF-B signalling can stop the growth of tumours. In light of these facts, an attempt is made to investigate binding characteristics of LOX inhibitors against 5-LOX (PDB-IDs 3V99 and 6N2W) and NF-κB (PDB-IDs 4KIK and 3DO7) through molecular docking, MM-GBSA calculation, molecular dynamic simulations (MDSs) and drug-likeness analysis. The eight lead molecules A169, A156, A162, A154, A102, A240, A86 and A58 were identified. The higher NF-B inhibiting potential of A169 was discovered through the sequential HTVS, SP docking and XP docking study. The hydrophobic interaction of Leu607, Phe610, Gln557 and Asn554 with 3V99 and Cys99, Glu97 and Arg20 of 4KIK is crucial for the inhibition. The LE, LLE and FQ values of A169 suggest their optimal binding with the target. This study strongly suggests the LOX and NF-κB inhibitory potential of A169, further lead optimisation and biological validation requires for the confirmations.Communicated by Ramaswamy H. Sarma.

Metal-Organic Framework in Pharmaceutical Drug Delivery.

Metal-organic frameworks (MOFs) are porous, crystalline materials made up of organic ligands and metal ions/metal clusters linked by coordinative bonds. This large family is becoming increasingly popular for drug delivery due to their tuneable porosity, chemical composition, size and shape, and ease of surface functionalization. There has been a growing interest over the last decades in the design of engineered MOFs with controlled sizes for a variety of biomedical applications. Starting with the MOFs classification adapted for drug delivery systems (DDSs) based on the types of constituting metals and ligands. MOFs are appealing drug delivery vehicles because of their substantial drug absorption capacity and slow-release processes, which protect and convey sensitive drug molecules to target areas. Other guest materials have been incorporated into MOFs to create MOF-composite materials, which have added additional functionalities such as externally triggered drug release, improved pharmacokinetics, and diagnostic aids. Magnetic nanoparticles in MOFs for MRI image contrast and polymer coatings that increase blood circulation time are examples of synthetically adaptable MOF-composites. By including photosensitizers, which exert lethal effects on cancer cells by converting tumour oxygen into reactive singlet oxygen (1O2), metalorganic frameworks have been employed for photodynamic treatment (PDT) of malignancies among a multitude of nanosized therapies. Importantly, a variety of representative MOF applications are described from the perspectives of pharmaceutics, disease therapy, and advanced drug delivery systems. However, because of their weak conductivity, selectivity, and lack of modification sites, MOF materials' uses in electrochemical biosensing are restricted. MOF-based composites provide excellent electrical conductivity and robust catalytic activity by adding functionalized nanoparticles into MOF structures, which process benefits over single component MOFs.