The cases of bacterial multidrug resistance are increasing every year and becoming a serious concern for human health. Multidrug efflux pumps are key players in the formation of antibiotic resistance, which transfer out a broad spectrum of drugs from the cell and convey resistance to the host. Efflux pumps have significantly reduced the efficacy of the previously available antibiotic armory, thereby increasing the frequency of therapeutic failures. In gram-negative bacteria, the AcrAB-TolC efflux pump is the principal transporter of the substrate and plays a major role in the formation of antibiotic resistance. In the current work, advanced computer-aided drug discovery approaches were utilized to find hit molecules from the library of biogenic chalcones against the bacterial AcrB efflux pump. The results of the performed computational studies via molecular docking, drug-likeness prediction, pharmacokinetic profiling, pharmacophore mapping, density functional theory, and molecular dynamics simulation study provided ZINC000004695648, ZINC000014762506, ZINC000014762510, ZINC000095099506, and ZINC000085510993 as stable hit molecules against the AcrB efflux pumps. Identified hits could successfully act against AcrB efflux pumps after optimization as lead molecules.Communicated by Ramaswamy H. Sarma.

1,3,4-Oxadiazoles are a vital class of nitrogen-containing five-membered heterocycles that have drawn considerable attention due to their diverse pharmacological properties. These compounds exhibit a broad spectrum of biological activities, including anticancer, antibacterial, anti-inflammatory, anti-HIV, anti-tubercular, anti-diabetic, and antifungal effects. Their unique structural framework makes them highly valuable in drug discovery and medicinal chemistry. This review provides a comprehensive overview of the various synthetic strategies employed to develop 1,3,4-oxadiazole derivatives. Both conventional and advanced methods are discussed in detail, including the cyclization of hydrazides, oxidative cyclization, and environmentally friendly green chemistry approaches. Additionally, we highlight how structural modifications influence their bioactivity, paving the way for the design of more potent therapeutic agents. Beyond synthesis, this paper explores the pharmacological evaluation of 1,3,4-oxadiazoles through various biological assays. The relationship between molecular structure and biological activity is examined, offering valuable insights into the rational design of novel derivatives with enhanced efficacy and selectivity. Given their versatility as a privileged scaffold in medicinal chemistry, 1,3,4-oxadiazoles hold significant promise in the development of new treatments for various diseases. Overall, this review serves as a valuable resource for researchers interested in the synthesis and therapeutic potential of 1,3,4-oxadiazole derivatives, aiding in the development of innovative drugs with improved pharmacological properties.

Pellets are small free flowing; spherical particulates manufactured by the agglomeration of fine powder or granules. Different types of techniques used to produce pellets are referred to as pelletization techniques. In relation to pharmaceuticals, pellets offer high degree of flexibility in design and development of oral dosage form. They offer desired dose strength, can be blended to deliver incompatible bioactive agents and can be blended to provide different release profiles. The most commonly use pelletization processes are Extrusion spheronization, Hot melt extrusion, Solution or suspension layering, Powder layering, High shear pelletization, Freeze pelletization, Cryopelletization, Crystallo-co-agglomeration, Wet spherical agglomeration, Spherical crystallization etc. In present review we will be explaining widely used pelletization techniques especially are Extrusion Spheronization and Hot Melt Extrusion in detail with methods and applications in pharmaceutical industries because these techniques represent an efficient pathway for novel drug delivery system today.