Design, synthesis and tubulin polymerization inhibition activity of newly synthesized hydrazone-linked to combretastatin analogues as potential anticancer agents

Synthesis, Characterization and Biological Evaluation of New Enamide Fluorinated‐Schiff Base Derivatives as Potential Cytotoxic and Apoptosis‐Inducing Agents

“…Therefore, the percentage inhibition of β‐tubulin polymerization after treatment with enamide‐furfural Schiff base compound 5 demonstrated that the molecular target of this compound was most likely tubulin and interferes with microtubule polymerization. It is worth mentioning that tubulin polymerization inhibitory result was in line with previous reported study [2] …”

“…Finally, the presence of benzofused ring such as indole in compound 7 (IC 50 =20.32 μM) led to reduction of the cytotoxic activity. Comparing the in vitro cytotoxic activity of the synthesized furfural Schiff base (the most active hybrid) with the previously reported lead molecule, indicated that furfural Schiff base 5 had a more cytotoxic impact (IC 50 =2.06 μM) on MCF‐7 breast cancer cells than the previously lead molecule (IC 50 =4.02 μM) [2] . In addition, except for enamide‐Schiff base compounds 3 and 4 d , the activity of the current enamide‐Schiff base hybrids (IC 50 =33.50–2.06 μM) is higher than that of the majority of previously published ones.…”

“…Refluxing of the methyl acrylate ester 1 with hydrazine hydrate in methanol afforded the main hydrazide derivative 2. [27] The acetaldehyde Schiff base 3 was prepared by heating at reflux of the hydrazide 2 with acetaldehyde in methanolic solution for 6 h. [2] In its 1 H-NMR, signals for the protons of the amide and hydrazone NH groups appeared at δ 10.04 and 9.93 ppm, respectively as singlet signals, while that for the azomethine protons (CH=N) appeared at δ 9.86 ppm. Besides, characteristic signal at δ 7.34 ppm appeared as singlet peak integrating the two protons of the trimethoxyphenyl ring.…”

“…Breast cancer is the most prominent cancer in women and considered the leading cause of cancer‐related death worldwide [1,2] . In general, the effectiveness of new cancer therapies is dependent on identifying functional targets that are required for tumor development and survival [3] .…”

“…Breast cancer is the most prominent cancer in women and considered the leading cause of cancer-related death worldwide. [1,2] In general, the effectiveness of new cancer therapies is dependent on identifying functional targets that are required for tumor development and survival. [3] In this regard, tubulin-microtubule dynamics have proven to be indispensable target for therapeutic intervention targeting, resulting in a significant breakthrough in the field of breast cancer.…”