Multicomponent Synthesis of Some Molecular Hybrid Containing Thiazole Pyrazole as Apoptosis Inducer

Abstract

The present study describes a multicomponent synthesis of molecular hybrid containing pyrazole, thiazole moiety using hydrazone as a linker, which have been synthesized by condensation of 1-phenyl-3-(aryl)-1H-pyrazole-4-carbaldehydes 1A-B: , thiosemicarbazide and α-bromoketones 2A-C: .The target hybrid compounds, 1-((1-phenyl-3-aryl-1H-pyrazole-4-yl)methylene)-2-(4-arylthiazole-2-yl)hydrazine 3A-F: are characterized by H-NMR,C NMR, FT-IR and mass. Apoptosis inducing ability and cytotoxic nature of all the hybrid compounds having thiazole, pyrazole and hydrazone were assessed by using biological assays viz morphological, fluorescence and tunel assays on granulosa cells of ovarian antral follicles of goat (Capra hircus) in vitro. Apoptosis was recognized and quantified using differential staining of ethidium bromide and acridine orange where apoptotic cells exhibited red fluorescence and live normal cells with intact cell membrane and normal nucleus displayed bright green fluorescence. Among the tested compounds, compound 3E: and 3B: showed the maximum potency to induce apoptosis with percentage of apoptosis 25.61±2.95and 23.45±1.46 respectively followed by 3F: (20.95±0.40) and 3D: (20.44±1.60) in comparison with control (5.14±0.44).

Recent Applications of the Multicomponent Synthesis for Bioactive Pyrazole Derivatives

“…The multicomponent synthesis of highly functionalized N -heterocycles as apoptosis inducers has been successfully implemented. For instance, a mixture of 3-aryl-1-phenyl-1 H -pyrazole-4-carbaldehydes 31 , thiosemicarbazide 23 , and α -bromoacetophenones 36 in refluxing ethanol for 5 min afforded a series of ( E )-2-(2-((3-aryl-1-phenyl-1 H -pyrazol-4-yl)methylene)hydrazinyl)-4-arylthiazoles 100 ( Scheme 6 ) [ 99 ]. The solids were filtered and recrystallized from ethanol to afford pyrazole derivatives with high yields and short reaction times.…”

Thymoquinone induces apoptosis in temozolomide‐resistant glioblastoma cells via the p38 mitogen‐activated protein kinase signaling pathway

“…Furthermore, MGMT expression was not significantly different between groups, hinting that neither TQ nor TMZ effectively alter MGMT expression in U251R cells. TQ is found to induce apoptosis, and this phenomenon might be responsible for its genotoxicity (DNA fragmentation assessed by TUNEL and DAPI) 29–32 . TUNEL‐DAPI staining confirmed that TQ alone and TQ combined with TMZ caused apoptosis in xenograft tumors (Figure 5B).…”

A Serendipitous Synthesis: SiO2‐HNO3 Mediated Oxidative Aromatization and Regioselective Nitration of 1,3,5‐Trisubstituted‐4,5‐Dihydro‐1H‐Pyrazoles

“…The attractiveness of pyrazoles and their derivatives is the versatility that allows the synthesis of a series of analogues with different moieties in them. In medicines, pyrazole is found as a pharmacophores in some bioactive molecules and play a role as antimalarial, anticancer, apoptosis inducer, antimicrobial, analgesic, antidiabetic, anticonvulsant, psychoanaleptic, CNS and antiangiogenic agents. The pyrazole moiety is also present in many agrochemical significant compounds, such as pesticides and insecticides such as cyenopyrafen, tebufenpyrad, tolfenpyrad and fenpyroximate .…”