Inhibition of Human Colorectal Cancer by a Natural Product 7-Acetylhorminone and Interactions with BSA/HSA: Multispectral Analysis and In Silico and In Vitro Studies.

We have semi-synthesized a natural product 7-acetylhorminone from crude extract of Premna obtusifolia (Indian headache tree), which is active against colorectal cancer after probation through computational screening methods as it passed through the set parameters of pharmacokinetics (most important nonblood-brain barrier permeant) and drug likeliness (e.g., Lipinski's, Ghose's, Veber's rule) which most other phytoconstituents failed to pass combined with docking with EGFR protein which is highly upregulated in the colorectal carcinoma cell. The structure of 7-acetylhorminone was confirmed by single crystal X-ray diffraction studies and 1H NMR, 13C NMR, and COSY studies. To validate the theoretical studies, first, in vitro experiments were carried out against human colorectal carcinoma cell lines (HCT116) which revealed the potent cytotoxic efficacy of 7-acetylhorminone and verified preliminary investigation. Second, the drugability of 7-acetylhorminone interaction with serum albumin proteins (HSA and BSA) is evaluated both theoretically and experimentally via steady-state fluorescence spectroscopic studies, circular dichroism, isothermal titration calorimetry, and molecular docking. In summary, this study reveals the applicability of 7-acetylhorminone as a potent drug candidate or as a combinatorial drug against colorectal cancer.

Bioinformatics and Network Pharmacology of the First Crystal Structured Clerodin: Anticancer and Antioxidant Potential against Human Breast Carcinoma Cell.

Clerodin was isolated from the medicinal plant Clerodendrum infortunatum, and CSD search showed the first crystal structure of clerodin by a single-crystal X-ray diffraction study. We checked its binding potential with target proteins by docking and conducted network pharmacology analysis, ADMET analysis, in silico pathway analysis, normal mode analysis (NMA), and cytotoxic activity studies to evaluate clerodin as a potential anticancer agent. The cell viability studies of clerodin on the human breast carcinoma cell line (MCF-7) showed toxicity on MCF-7 cells but no toxicity toward normal human lymphocyte cells (HLCs). The anticancer mechanism of clerodin was validated by its enhanced capacity to produce intracellular reactive oxygen species (ROS) and to lower the reduced glutathione content in MCF-7 cells.

Synthesis and characterization of biogenic metal nanoparticles and its cytotoxicity and anti-neoplasticity through the induction of oxidative stress, mitochondrial dysfunction and apoptosis.

In the present study, we demonstrate a simple, cost-effective and eco-friendly method for biogenic synthesis of silver nanoparticles (AgNPCGs) using ethanolic extract of Calotropis gigantea latex. Attempts were made to characterize these biogenic silver nanoparticles AgNPCGs and also to test its cytotoxic, anti-neoplastic and apoptotic potential through the induction of oxidative stress, mitochondrial dysfunction. AgNPCGs were characterized by UV-vis spectroscopy, dynamic light scattering (DLS) and surface zeta potential measurement, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM) and selected area electron diffraction, scanning electron microscopy (SEM), energy-dispersive X-ray fluorescence spectrometry (EDX). UV visible spectroscopy showed an intense surface plasmon resonance band at 431nm which clearly reflected the formation of silver nanoparticles. FTIR study revealed that latex extract acted as reducing and stabilizing agent for the synthesis of AgNPCGs. Energy dispersive X-ray spectroscopy confirmed the presence of silver as a major component of synthesized AgNPCGs. SEM and TEM studies showed that the synthesized AgNPCGs were nearly spherical in shape with an average size of 2.338nm. The selected area electron diffraction pattern and XRD studies confirmed the crystalline nature of AgNPCGs. AgNPCGs exhibited in-vitro cytotoxic activity against Ehrlich's ascites carcinoma (EAC), Jurkat and MCF-7 cells at respective IC50 doses without producing cytotoxicity to mice and human lymphocytes. Significant chromatin condensation, DNA fragmentation, cell cycle arrest at G2/M phase, up-regulation of Bax and caspase-3 and down-regulation of Bcl-2 were observed in AgNPCGs treated EAC cells. The results suggest that biogenic silver nanoparticles AgNPCGs could be a potential chemotherapeutic formulation for cancer therapy.