Deciphering the key heterocyclic scaffolds in targeting microtubules, kinases and carbonic anhydrases for cancer drug development

Multitargeting approaches involving carbonic anhydrase inhibitors: hybrid drugs against a variety of disorders

“…Some of the most widely used anticancer drugs nowadays are the tyrosine kinase inhibitors and the tubulin polymerisation inhibitors, with many new representatives of these classes being launched each year 69 . Thus, in this paragraph I will examine a set of hybridisation approaches which involve CAIs and several other, rather heterogeneous classes of antitumor agents, among which the epidermal growth factor receptor (EGFR) antagonists (this protein has kinase activity) 70 , the 15-lipoxygenase (15-LOX)/COX-2 (multitargeting of tree different proteins) inhibitors 71 , the telomerase inhibitors 72 , the P-glycoprotein (P-gp) inhibitors 73 , and the thioredoxin inhibitors 74 , 75 .…”

“…Zhang et al. 70 reported hybrids incorporating the tyrosine kinase inhibitory fragments found in erlotinib and gefitinib, clinically used anticancer agents 69 and benzenesulphonamides with CA inhibitory activity, of types 36 ( Figure 13 ) which were shown to possess antiproliferative activity against several cell lines, such as A549, A431 and H1975. Few of the compounds were also tested for the inhibition of EGFR (wild type and mutant) and hCA II and IX, showing nanomolar activity for the first protein, and micromolar ones for the CAs.…”

Design and Synthesis of Newly Synthesized Acrylamide Derivatives as Potential Chemotherapeutic Agents against MCF-7 Breast Cancer Cell Line Lodged on PEGylated Bilosomal Nano-Vesicles for Improving Cytotoxic Activity

“…4-(furan-2ylmethylene)-2-(3,4,5-trimethoxyphenyl)oxazol-5(4H)-one (1) is the starting material and was prepared by condensation of 2-(3,4,5-trimethoxybenzamide)acetic acid, furfural and acetic anhydride in the presence of anhydrous sodium acetate in an oil bath at 80-100 • C according to literature reported [25]. The structure of the starting oxazolone 1 was confirmed by IR, 1 H-NMR and 13 C-NMR spectra. IR spectrum of oxazolone 1 showed the characteristic C=O stretching absorption of lactone ring at ν 1805 cm −1 .…”

“…The structures of compounds 4a-e were confirmed using IR and NMR spectra. 1 H-NMR spectrum of compound 4c as a representative example showed the presence of characteristic two exchangeable proton (2NH) at δ 9.94 ppm. The 13 C-NMR spectrum of compound 4c showed the presence of extra signals related to aromatic carbons.…”

“…Microtubules are one of the most important cellular protein scaffolds [1,2]. Microtubules along with actin and intermediate filaments are major cell building blocks and, therefore, play an integral role in cell reproductive processes during mitosis [3,4].…”