Design, Synthesis, In Silico Studies and In Vitro Anticancer Activity of 3‐(4‐Methoxyphenyl)azetidine Derivatives

Abstract

A series of 3‐(4‐methoxyphenyl)azetidine analogues were synthesized and screened for their in vitro anticancer activity against nine different human cancer cell lines using the cell counting kit‐8 (CCK‐8) assay. The synthesized molecules were characterized by 1H NMR, 13C NMR, LCMS and IR analysis. The toxicity, bioavailability and lipophilicity of all the synthesized compounds were predicted by using osiris and molinspiration model. Molecular docking study revealed that, compound 6‐(3‐(3‐(2‐aminopyridin‐4‐yl)‐4‐methoxyphenyl)azetidin‐1‐yl)picolinonitrile (4 A‐17) and 6‐(3‐(4‐methoxy‐3‐(2‐methoxypyridin‐4‐yl)phenyl)azetidin‐1‐yl)picolinonitrile (4 A‐19) were found to be potential inhibitor of human topoisomerase IIα. The cell viability studies exhibited promising antiproliferative activities of the novel synthesized compounds. 4 A‐17 (EC50 0.03 μM) was found to be more potent than standard Doxorubicin (EC50 0.07 μM) in U251 cancer cell lines. Similarly, 4 A‐19 showed considerable potency against four different cancer cell lines (HepG2, U251, A431, 786‐O) with EC50 values ranging from 0.46 to 2.13 μM. These primary findings supported that molecule 4 A‐17 and 4 A‐19 should be subjected to further studies and lead optimization.

Synthesis, Characterization, Molecular Docking and in vitro Anticancer Screening of Some Novel Thiophene Derivatives

“…cell lines were seeded in 96 well plate and incubated for 24 h to achieve its morphology as showed in Figure 1. Post CCK 8 assay [43] it was observed that the ethyl 2‐(2‐(4‐((2‐ethoxyphenyl)carbamoyl)piperazin‐1‐yl)acetamido)‐5‐methyl‐4‐phenylthiophene‐3‐carboxylate (AP‐C12) extract showed highest inhibition in U87‐MG cell line. The inhibition was compared with the positive control Temozolomide.…”

“…cell lines were seeded in 96 well plate and incubated for 24 h to achieve its morphology as showed in Figure 1. Post CCK 8 assay [43]…”

Design, synthesis, and in silico study of hybrid oxoazetidine conjugated thiazoles as anti‐EGFR with cytotoxicity activity

“…Thus, their design and synthesis serve as a key part of synthetic chemical research. [ 33 ] In among varieties of heterocycles, azetidines constitute a vital and very significant place but the least explored group. The azetidine skeletons displayed a good balance between molecular rigidity and stability.…”

“…[ 33,34 ] This ring permits an effectual modification of pharmacological properties [ 35 ] and that's why azetidine serves as a core part of many existing drugs such as azelnidipine, tebanicline, delafloxacin, baricitinib, cobimetinib, and tebipenem. [ 33 ] In the earlier research, [ 36 ] it was illustrated that azetidine moiety as a linker with phenyl ring act as a pharmacophore. Thiazole‐containing skeletons are one of the most revered skeletons and key pharmacophores with many applications and pharmacological activities attributed to them such as antimicrobials, [ 37 ] antioxidant, [ 38 ] anticandida and cytotoxicity, [ 39 ] and anti‐inflammatory.…”

“…The azetidine skeletons displayed a good balance between molecular rigidity and stability. [33,34] This ring permits an effectual modification of pharmacological properties [35] and that's why azetidine serves as a core part of many existing drugs such as azelnidipine, tebanicline, delafloxacin, baricitinib, cobimetinib, and tebipenem. [33] In the earlier research, [36] it was illustrated that azetidine moiety as a linker with phenyl ring act as a pharmacophore.…”