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.

Exploring the Propensities of Fluorescent Carbazole Analogs toward the Inhibition of Amyloid Aggregation in Type 2 Diabetes: An Experimental and Theoretical Endeavor.

Amyloid aggregation is a pathological trait observed in many incurable and fatal neurodegenerative and metabolic diseases associated with misfolding and self-assembly of various proteins. Noncovalent interactions between these structural motifs and small molecules can, however, prevent this aggregation. Herein, five structurally different synthetic (Cz1-Cz4) and naturally occurring (Cz5, mahanimbine) fluorescent carbazole analogs are explored for their comparative amyloid aggregation inhibitory activities. Cz3 inhibited the amyloid deposition on the pancreatic ß-cells of diabetic mice. Moreover, Cz3 and Cz5 also showed efficacy as the fluorescent cell (MIN6) imaging agents. Further structural modifications of these carbazoles may lead to development of low-cost and non-toxic therapeutic agents for Type 2 diabetes and other amyloidosis-related diseases.