Synthesis and Cytotoxicity Evaluation of New 3‐substituted 4‐(4‐methyloxy phenyl)‐1H‐Pyrrole Derivatives

Abstract

A new series of 3‐substituted 4‐(4‐methyloxy phenyl)‐1H‐pyrrole derivatives were synthesized and biologically evaluated for potential anticancer activity. Fifteen targeted compounds showed high selectivity toward normal cells and cancer cells: that is, all targeted compounds had no obvious cytotoxicity toward normal human cells (HUVEC and NIH/3T3), but some compounds exhibited broad‐spectrum proliferation inhibitory activity against the screened cancer cell lines. Among these pyrrole derivatives, compounds 3b and 3o showed potent anticancer activity against the MG‐63 cell line, with IC50 values of 14.9 and 12.7 μM, respectively. Other pyrrole derivatives also showed promising proliferation inhibitory activity, including compound 3d against A375 (IC50 = 18.6 μM), compound 3f and 3j against MGC80‐3 (IC50 = 19.9 μM), and compound 3o against MGC80‐3 (IC50 = 11.9 μM). Because the developed pyrrole derivatives showed strong anticancer activity and high selectivity, this new series of pyrrole derivatives could be considered as promising lead compounds for further development of potent and safe anticancer agents.

Synthesis of 3-Aroyl-4-heteroarylpyrrole Derivatives by the Van Leusen Method

“…In the 1 H NMR spectrum for compound 8a, the signals appeared at 7.02, 70.9, and 11.61 ppm; in 8b at 7.04, 7.24, and 11.57 ppm; in 8c at 7.04, 7.19, and 11.62 ppm. IR, 13 C-NMR, and HR-MS analyses further established the structures of all of the 8 compounds (Original spectra are available in the Supplementary Materials section).…”

“…The chemical nature of TosMIC provides three different reactive sites because of the functional groups (an isocyanide group, a sulfonyl group, and an active methylene group). In reaction to the structural diversity of heterocyclic analogs of chalcones [9,10], TosMIC allows access to the polysubstituted or condensed pyrrole derivatives with different types of substituents-simple or complex-and has potential applications in the fields of chemistry and medicine [11][12][13].…”

“…δ (ppm): 2.64 (s, 3H, CH 3 ), 7.04 (s, 1H, H5, pyrrole), 7.19 (s, 1H, H2, pyrrole), 7.24 (t, 2H, Hm, 3-aroyl), 7.26 (t, 2H, Hp, Ph-pyrazolopyridine, J = 7.5 Hz), 7.36-7.53 (m, 9H, Hm, Phpyrazolopyridine; Ho, Hm, 3-aroyl; Hm, Hp, Ph-3-aroyl), 7.62 (d, 2H, Ho, 6-aryl, J = 8.5 Hz), 7.65 (d, 2H, Hm, 6-aryl, J = 8.5 Hz), 8.25 (s, 1H, H4, pyrazolopyridine), 8.31 (d, 2H, Ho Phpyrazolopyridine, J = 8.5 Hz), 11.62 (s, 1H, NH) 13. C-NMR δ (ppm): 12.6 (CH 3 ), 116.0 (C3a pyrazolopyridine), 120.0 (Co, Ph-pyrazolopyridine), 120.8 (C2, pyrrole), 122.4 (C5, pyrazolopyridine), 123.5 (C4, pyrrole), 125.1 (C3, pyrrole), 125.5 (Cp, Ph-pyrazolopyridine), 126.5 (Cp, 3-aroyl), 127.3 (Co, 3-aroyl), 127.8 (Co, 3-aroyl), 128.5 (Cm, 6-aryl), 129.5 (Cm, 3-aroyl), 129.6 (Cm, Ph-pyrazolopyridine), 129.7 (Co, 6-aryl), 131.8 (C4 pyrazolopyridine), 132.3 (C5, pyrrole), 133.1 (Ci, 6-aryl), 138.5 (Ci, Ph-pyrazolopyridine), 139.7 (Ci, Ar-pyrazolopyridine), 139.8(Ci, 3-aroyl), 139.9(Ci, 3-aroyl), 143.1 (Cp, 3-aroyl), 143.2 (C3, pyrazolopyridine), 149.7 (C7a, pyrazolopyridine), 157.0 (C6 pyrazolopyridine), 189.4 (C=O).…”

Recent Advances for the Synthesis of N‐Unsubstituted Pyrroles

“…[90] A new series of 3-substituted 4-(4-methyloxy phenyl)-1Hpyrrole derivatives 279 were synthesized by the group of Zhenmin Mao (Scheme 93). [91] It should be noted that, in contrast to the previous example, a stronger base was used in this reaction. Pyrroles 279 a-o were obtained in order to assess their biological activity.…”

Solvent Free Three-Component Synthesis of 2,4,5-trisubstituted-1H-pyrrol-3-ol-type Compounds from L-tryptophan: DFT-B3LYP Calculations for the Reaction Mechanism and 3H-pyrrol-3-one↔1H-pyrrol-3-ol Tautomeric Equilibrium

“…Within this type of compounds, 1 H -pyrrole is representative since it is well-known as a fundamental structural subunit in many of the naturally-occurring biological agents [ 2 ]. From this fact, many synthetic pyrrole derivatives have been obtained on the basis of biomimetic exercises, and have shown promissory behavior as antipsychotics, adrenergic antagonists, anxiolytics, anticancer, antibacterial and antifungal agents [ 3 , 4 , 5 ]. For example, synthetic 1,5-diphenylpyrrole-type compounds have shown high activity against a panel of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa y Enterobacter cloacae (ESKAPE) bacteria, similar to or even better than levofloxacin, a widely known antibiotic [ 6 ].…”