A novel series of natural compound-caffeic acid derivatives were synthesized by coupling with different substituted amines and alkyl halides in an effort to enhance the anticancer activity and explore the structure-activity relationship. The structures of the compounds were determined by 1H NMR and mass spectroscopy analysis. Compounds were evaluated for inhibition against HeLa-cervical cancer cell proliferation and results revealed that compound (E)-N-(4-cyanobenzyl)-3-(3,4- dihydroxyphenyl)acrylamide (SHC5) exhibited potent antiproliferative activity with 5.2 μM concentration and it is further confirmed by Hoechst/PI double staining and Annexin V/PI double staining assay. Further, compound SHC5 was screened against other cancer cell lines namely K562, Jurkat, HCT116 and MiaPaCa2 to test the specificity of the molecule and found to be ineffective.

The vital role played by microtubules in the cell division process, marks them as a potential druggable target to decimate cancer. A novel furan-2-carboxamide based small molecule, is a selective microtubule stabilizing agent (MSA) with IC50 ranging from 4 mu M to 8 mu M in different cancer cell lines. Inhibition of tubulin polymerization or stabilization of tubulin polymers abrogates chromosomal segregation during cell division, results in cell cycle arrest and leads to cell death due to the delayed repair mechanism. A novel furan-2-carboxamide based small molecule exhibited potent anti-proliferative and anti-metastatic property In-Vitro against the panel of cancer cells. Annexin V-FITC/PI, double staining reveals potent cytotoxic effect of SH09 against HeLa cells. FACS analysis displays induction of G2/M arrest and accumulation of subG1 population of cells upon treatment with SH09. Molecular docking study unveils SH09 binding affinity to the Taxol binding pocket of tubulin proteins and MM-GBSA also confirms strong binding energies of SH09 with tubulin proteins.

In the past, several microtubule targeting agents (MTAs) have been developed into successful anticancer drugs. However, the usage of these drugs has been limited by the acquisition of drug resistance in many cancers. Therefore, there is a constant demand for the development of new therapeutic drugs. Here we report the discovery of 5-5 (3-cchlorophenyl)-N-(3-pyridinyl)-2-furamide (CPPF), a novel microtubule targeting anticancer agent. Using both 2D and 3D culture systems, we showed that CPPF was able to suppress the proliferation of diverse cancer cell lines. In addition, CPPF was able to inhibit the growth of multidrug-resistant cell lines that are resistant to other MTAs, such as paclitaxel and colchicine. Our results showed that CPPF inhibited growth by depolymerizing microtubules leading to mitotic arrest and apoptosis. We also confirmed CPPF anticancer effects in vivo using both a mouse xenograft and a two-step skin cancer mouse model. Using established zebrafish models, we showed that CPPF has low toxicity in vivo. Overall, our study proves that CPPF has the potential to become a successful anticancer chemotherapeutic drug.

ABSTRACT Adipogenesis is a key driver of the expansion of adipose tissue mass that causes obesity. Hirsutenone (HST) is an active botanical diarylheptanoid present in Alnus species. In this study, we evaluated the effects of HST on adipogenesis, its mechanisms of action and the molecular targets involved. Using Oil Red O staining, we observed that HST dose‐dependently suppresses lipid accumulation during adipogenesis in 3T3‐L1 preadipocytes, concomitant with a decrease in peroxisome proliferator‐activated receptor‐γ (PPARγ), CCAAT/enhancer‐binding protein α (C/EBPα) and fatty acid synthase (FAS) protein expression. This inhibitory effect was largely limited to the early stage of adipogenesis, which includes mitotic clonal expansion (MCE), as evidenced by delayed cell cycle entry of preadipocytes from G1 to S phase. Furthermore, the regulation of MCE was accompanied by suppression of phosphatidylinositol 3‐kinase (PI3K) and extracellular‐regulated kinase (ERK) activity. HST was also shown to bind directly to PI3K and ERK1 in a non‐ATP competitive manner. Our results suggest that HST attenuates adipogenesis by directly targeting PI3K and ERK during MCE in 3T3‐L1 preadipocytes, underscoring the potential therapeutic application of HST in preventing obesity. J. Cell. Biochem. 116: 1361–1370, 2015. © 2015 Wiley Periodicals, Inc.