Inspired by the well-documented tumor protecting ability of paullones, recently, we synthesized novel paullone-like scaffolds, indole-fused benzo-oxazepines (IFBOs), and screened them against hepatocellular carcinoma (HCC) specific Hep-G2 cells. Three of the synthesized compounds significantly attenuated the progression of HCC in vitro. By computational studies, we further discovered that IFBOs exhibited a stable binding complex with the IL-6 receptor. In this context, we investigated in vivo study using the nitrosodiethyl amine (NDEA)-induced HCC model, which strengthened our previous findings by showing the blockade of the IL-6 mediated JAK2/STAT3 oncogenic signaling pathway. Treatment with IFBOs showed remarkable attenuation of cellular proliferation, as evidenced through a decrease in the number of nodules, restoration of body weight, oxidative stress parameters, liver marker enzymes and histological architecture. Interestingly, using a metabolomic approach we further discovered that IFBOs can restore the perturbed metabolic profile associated with the HCC condition to normalcy. Particularly, the efficacy of compound 6a for an anti-HCC response was significantly better than the marketed chemotherapeutic drug, 5-fluorouracil. Altogether, these remarkable findings open up possibilities of developing IFBOs as novel future candidate molecules for plausible alternatives for HCC treatment.

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In this paper, we have proposed and analyzed a nonlinear mathematical model for the study of interaction between tumor cells and oncolytic viruses. The model is analyzed using stability theory of differential equations. Positive equilibrium points of the system are investigated and their stability analysis is carried out. Moreover, the numerical simulation of the proposed model is also performed by using fourth order RungeKutta method which supports the theoretical findings. It is found that both infected and uninfected tumor cells and hence tumor load can be eliminated with time, and complete recovery is possible because of virus therapy, if certain conditions are satisfied. It is further found that the system appears to exhibit periodic limit cycles and chaotic attractors for some ranges of the system parameters.

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