Quinazolino linked 4β-amidopodophyllotoxin conjugates regulate angiogenic pathway and control breast cancer cell proliferation

Design, synthesis, biological evaluation, and 3D‐QSAR analysis of podophyllotoxin–dioxazole combination as tubulin targeting anticancer agents

“…As the primary target of modification, massive agents have been derived from the C‐4 site of podophyllotoxin to be implemented in clinics . According to SAR (the structure–activity relationship), C‐4 position is capable of resisting large groups, so it has great potential in functionalization . It is widely recognized that 1,3,4‐oxadiazole is a large group of heterocyclic compounds which has been discovered to reveal antitumor activities .…”

Click chemistry‐based synthesis and cytotoxic activity evaluation of 4α‐triazole acetate podophyllotoxin derivatives

“…Clearly, these preliminary data further confirmed that compound 31 could induce apoptosis in PC‐3 cancer cells. In addition to the currently mentioned proteins, derivatives of PPT have also been reported to inhibit tumor cell proliferation or induce tumor cell death by regulating a series of other apoptosis‐related proteins such as DNA topoisomerase‐I, DNA topoisomerase‐II, DNA topoisomerase‐IIα, NF‐κB, ERK, JNK, P16, P21, P38, P51, and caspases (Kamal et al., , , , , ; Lin, Huang, Chen, Lee, & Huang, ; Liu et al., ; Zhang et al., , ). Therefore, more detailed mechanistic investigations on newly synthesized derivatives are also needed and our bioactive probe‐based cellular target identification of PPT via dansyl‐PPT ( 34 ) and biotin‐PPT ( 35 ) are currently ongoing and will be disclosed in due time.…”

Synthesis and Cytotoxicity of Novel Analogues of Podophyllotoxin

“…Thefour derivatives of podophyllotoxin namely the chalcone derivatives, 2-benzylidene-6, 7-dimethoxy-4-phenyl-3, 4-dihydro-2H-naphthalen-1-one (4a) and 2-benzylidene-5, 7-dichloro-6-hydroxy-4-phenyl-3, 4-dihydro-2H-naphthalen-1-one (4b) and aminothiazolyl derivatives, 7,8-dimethoxy-5-phenyl-4,5-dihydro-naphtha[1,2-d] thiazol-2-yl amine (5a) and 2-amino-6,8-dichloro-5-phenyl-4,5-dihydro-naphtho[1,2-d] thiazol-7-ol (5b) were synthesized and compared for their ability to induce cytotoxicity. Recent reports on podophyllotoxin derivatives suggest that they can be potential anti-tumor drugs by the induction of apoptosis and inhibiting tumor angiogenesis [20] [18]. The in vitro cell based cytotoxicity assay is a useful and reliable method to demonstrate the activity of chemotherapeutic drugs and also gives a prior knowledge of the efficacy of various agents before using in invivo [21].The Ehrlich Ascites tumor is a murine mammary adenocarcinoma which grows in mice by intra peritoneal passages.…”

“…The 2-amino derivatives of thiazoles possess anti-cancer activity by the inhibition of kinases [14] [15]. The chalcones are also an important class of compounds which are extensively investigated for a wide range of biological activity like anti-inflammatory [16], antitumor [17] and antibacterial [18] properties.Our interest in synthesizing the podophyllotoxin derivatives stems from the fact that the aminothiazolyl derivatives and chalcone derivatives of lignans can add to the therapeutic value of podophyllotoxin derivatives.Hence we designed the study to synthesize novel derivatives with greater therapeutic efficacy and evaluate theircytotoxicity and potencyin murine mammary carcinoma cells in an in vitro system.…”