Tumor Necrosis Factor Alpha (TNF-α) is a pleiotropic pro-inflammatory cytokine. It act as central biological regulator in critical immune functions, but its dysregulation has been linked with a number of diseases. Inhibition of TNF-α has considerable therapeutic potential for diseases such as cancer, diabetes, and especially autoimmune diseases. Despite the fact that many small molecule inhibitors have been identified against TNF-α, no orally active drug has been reported yet which demand an urgent need of a small molecule drug against TNF-α. This study focuses on the development of ligand-based selective pharmacophore model to perform virtual screening of plant origin natural product database for the identification of potential inhibitors against TNF-α. The resultant hits, identified as actives were evaluated by molecular docking studies to get insight into their potential binding interaction with the target protein. Based on pharmacophore matching, interacting residues, docking score, more affinity towards TNF-α with diverse scaffolds five compounds were selected for in vitro activity study. Experimental validation led to the identification of three chemically diverse potential compounds with the IC50 32.5 ± 4.5 µM, 6.5 ± 0.8 µM and 27.4 ± 1.7 µM, respectively.

Three dimensional problems reflect more imperative understanding to real world issues in comparison to two dimensional problems. Keeping this fact in mind, a mathematical model is designed to deliberate the 3D magnetohydrodynamic couple stress nanofluid flow with joule heating and viscous dissipation effects past an exponential stretched surface. The analysis is performed keeping in mind the physical effects of Brownian motion and thermophoresis combined with convective heat condition. This paper also distinctly introduces a more realistic boundary constraint for nanoliquid flow model. For instance, zero mass flux condition has been instituted for the first time for 3D couple stress nanofluid model as far as the exponential stretched surface is concerned. Self-similar transformations are engaged to obtain a system of ordinary differential equations possessing high nonlinearity from the system of boundary layer partial differential equations. Analytic solution is constructed in the form of series using Homotopy Analysis Method (HAM). Numerically calculated values of Skin friction and local Nusselt number are also given with suitable analysis. Moreover, the influences of sundry parameters on velocity distribution, and heat and mass transfer rates are deliberated and depicted through relevant graphs. The results obtained clearly show that the Biot number and Hartmann number possess increasing effect on temperature distribution. To authenticate our obtained results, a comparison in limiting case is also given.

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