Design, synthesis and anticancer activities of halogenated Phenstatin analogs as microtubule destabilizing agent

Cytotoxic substituted indolizines as new colchicine site tubulin polymerisation inhibitors

“…Its biological properties are comparable to CA-4, currently investigated in clinical trials 16 , but in contrast to CA-4, Phenstatin has a greater pharmacological potential due to improved metabolic stability and requires an easier synthesis for large-scale production 17 . In the process of drug discovery, this kind of compounds are lead scaffolds for the development of improved bioactive analogues, and Phenstatin continues to be a source of inspiration for researchers in designing new potential anticancer drugs [18][19][20][21][22][23][24][25] .…”

Facile Approach toC‐Glucosides by Using a Protecting‐Group‐Free Hiyama Cross‐Coupling Reaction: High‐Yielding Dapagliflozin Synthesis

“…The required acceptor for the crosscoupling reaction was prepared via a published three-step synthesis. [23] According to the general procedure, 1-diisopropylsilyl-d-glucal 4 underwent the Hiyama cross-coupling reaction with the prepared 1-chloro-2-(4-ethoxybenzyl)-4-iodobenzene and the desired pseudo-C-glycoside 5 n (Table 2) was obtained in excellent 96 % yield. For the synthesis of dapagliflozin, 5 n was simply used for hydroboration-oxidation, which resulted in a molecule of dapagliflozin 7 n in 82 % isolated yield with exclusive β-anomeric stereoselectivity (Scheme 2).…”

“…The compatibility with various aromatic electrophiles enabled us to apply this Hiyama coupling reaction to the synthesis of dapagliflozin, a worldwide approved inhibitor for the treatment of type 2 diabetes. The required acceptor for the cross‐coupling reaction was prepared via a published three‐step synthesis [23] . According to the general procedure, 1‐diisopropylsilyl‐ d ‐glucal 4 underwent the Hiyama cross‐coupling reaction with the prepared 1‐chloro‐2‐(4‐ethoxybenzyl)‐4‐iodobenzene and the desired pseudo‐ C ‐glycoside 5 n (Table 2) was obtained in excellent 96 % yield.…”

Expedition of sulfur‐containing heterocyclic derivatives as cytotoxic agents in medicinal chemistry: A decade update

“…134 Similarly, phenstatin 90 is another molecule, which is a synthetic small molecule tubulin inhibitor, wherein the double bond of CA-4 is replaced with a carbonyl group. 135 Since benzene and thiophene are classical bioisosteres, novel thiophene derivatives as tubulin polymerization inhibitors were established by Romagnoli et al 136 These derivatives were validated substantial growth inhibitory effects against L1210 (murine leukemia), FM3A, and human T-lymphoblastoid Molt4 and CEM cells. Of the tested compounds, derivatives 91-94 (Figure 14) unveiled high potency against Murine Mammary Carcinoma (FM3A) tumor cell lines when compared with the standard drug CA-4 (Table 5).…”

“…Combretastatin (CA‐4) is a very well‐known naturally occurring molecule that binds at the colchicine site and inhibits the polymerization of tubulin 134 . Similarly, phenstatin 90 is another molecule, which is a synthetic small molecule tubulin inhibitor, wherein the double bond of CA‐4 is replaced with a carbonyl group 135 . Since benzene and thiophene are classical bioisosteres, novel thiophene derivatives as tubulin polymerization inhibitors were established by Romagnoli et al 136 These derivatives were validated substantial growth inhibitory effects against L1210 (murine leukemia), FM3A, and human T‐lymphoblastoid Molt4 and CEM cells.…”