Synthesis, biological evaluation, and docking studies of new pyrazole-based thiourea and sulfonamide derivatives as inhibitors of nucleotide pyrophosphatase/phosphodiesterase

Anticancer activity and QSAR study of sulfur-containing thiourea and sulfonamide derivatives

“…For the bis-sulfonamide derivatives (Type IV-VI, 24-38), 2,3,5,6-tetramethylphenyl derivative 25 as well as 4-chlorophenyl compounds 28 and 38 displayed a broad array of cytotoxic activities toward all the tested cells. Along the line, the 4-chloro derivative 28 was shown to be the most potent cytotoxic compound against HuCCA- All of the studied bis-sulfonamide derivatives (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38) have been disclosed to act as aromatase inhibitors except for compound 35 [20]. Additionally, some of these meta-bis-sulfonamides (i.e., 24, 27, 29, and 31) have been reported to induce apoptosis in various cancer cell lines.…”

“…In an area of anticancer drug discovery, thiourea and sulfonamide derivatives were reported to exhibit their anticancer actions via inhibiting diverse molecular targets such as tubulin [14,15], carbonic anhydrase [16,17], topoisomerase II [18], aromatase [19,20], cyclin-dependent kinase (CDK) [21], epidermal growth factor receptor (EGFR) [22,23], sirtuin [24], nucleotide pyrophosphatase/phosphodiesterase [25], v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) [26], and others. These suggested the potentials of these scaffolds to be promising pharmacophores for discovery of novel anticancer therapeutics.…”

Pyridine Moiety: Recent Advances in Cancer Treatment

“…Among the synthesized compounds, compound 11 was proved to be a potent PI3K/mTOR dual inhibitor with exceptional kinase selectivity, modest plasma clearance and acceptable oral bioavailability, with IC 50 0. Ullah et al [109] synthesized and evaluated a series of pyridine-pyrazole-benzenethiourea and pyridinepyrazole-benzenesulfonamide scaffold for their inhibitory effect on human nucleotide Ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) 1 and ENPP3 isoenzymes. Among them, compound 12a was the most potent inhibitor of ENPP3 (IC 50 =0.21 µM) and compound 12b was much selective to ENPP1 with IC 50 value of 0.40 µM and found promising cytotoxic against HeLa, MCF-7 and 1321N1 (Astrocytoma cell line) cell lines.…”

Synthesis and cytotoxicity against tumor cells of pincer N-heterocyclic ligands and their transition metal complexes

“…The synthesis of L rst involves the synthesis of pyrazolic ester 2-ethyl 5-methyl-1H-pyrazole-3-carboxylate (L pyz ), which is carried out in two steps, as reported previously by our group (Scheme 2). 15 The synthesis protocol and characterization of L 0 , 1 0 and 2 0 have been described in our previous work. 30 2.2.1 Synthesis of diethyl 1,1 0 -(pyridine-2,6-diyl) bis(5methyl-1H-pyrazole-3-carboxylate) (L).…”

“…Heterocyclic compounds containing pyrazole and pyridine were reported to show remarkable biological properties. 14,15 The pyrazole scaffold is a privileged pharmacophore encountered in many chemical compounds conrmed to be associated with various biological assets such as anti-inammatory, 16 antimicrobial and anticancer properties. 17,18 Furthermore, many compounds bearing a pyridine moiety have been identied to be biologically active [19][20][21][22] and therapeutically relevant in medicinal chemistry and to display versatile biological activities including antibacterial and anticancer activities.…”