Novel fluorinated curcuminoids and their pyrazole and isoxazole derivatives: Synthesis, structural studies, Computational/Docking and in-vitro bioassay

Recent Updates in Curcumin Pyrazole and Isoxazole Derivatives: Synthesis and Biological Application

“…[50] Numerous semicarbazone and pyrazole derivatives of curcumin have been synthesized as potential mitigation agents to cure acute radiation syndrome (ARS). [77] Water-soluble pyrazole curcumin derivative (PyCurOAc) was found to inhibit formation of advanced glycation end products (AGEs) better than curcumin. [74] Pyrazole curcumin derivatives demonstrated bioactivity and brain absorption to re-establish membrane integrity.…”

Deuterated Curcuminoids: Synthesis, Structures, Computational/Docking and Comparative Cell Viability Assays against Colorectal Cancer

“…In continuationo fo ur previous studies on novel curcuminoids (CUR) and CUR-BF 2 adducts, [8][9][10] and with the recentd iscovery of demethylation as an additional metabolic pathway in parentc urcumin, [6] we synthesized two libraries of deuterated CUR-BF 2 andC UR compounds, one bearing OCD 3 groups (Figure 2), and the other bearing halogenated phenyl rings and OCD 3 groups ( Figure 3), as modelst hat may exhibit improvedm etabolic stability via as econdary/remote deuterium isotope effect stemming from the demethylation pathway.T he ring-deuterated hexamethoxy-CUR-BF 2 and CUR compounds were also synthesized for comparison with their non-deuterated analogues.H erein we report their synthesis, structurals tudies (by X-ray analysis and DFT), computational/docking, and As eries of deuterated curcuminoids (CUR) were synthesized, bearing two to sixO CD 3 groups, in somec ases in combination with methoxy groups,a nd in others together with fluorine or chlorine atoms. Am odel ring-deuterated hexamethoxy-CUR-BF 2 and its corresponding CUR compound were also synthesized from a2 ,4,6-trimethoxybenzaldehyde-3,5-d 2 precursor.A s with their protio analogues,t he deuterated compounds were found to remain exclusively in the enolic form.…”

“…Attempts to prepare the ring-deuterated analogue of 3,4,5-benzaldehye using this procedure was unsuccessful even after prolonged reaction times, increasing temperature, or by using additional B(C 6 F 5 ) 3 .T his finding reinforces the suggested H/D mechanism, [11] because in this case the OMe groups cannot help stabilize the benzenium ion of ipso attack leading to H/D exchange. Using ap rocedure similar to that reported previously, [8,9] the ring-deuterated hexamethoxy-CUR-BF 2 adduct 15 was prepared by reacting the 3,5-d 2 -aldehyde (2.2 equiv) with acetylacetone-BF 2 complex (1 equiv) and nBuNH 2 (0.22 equiv) in ethyl acetate under nitrogen. Upon completion (monitored by TLC) the product was vacuum filtered, washed with ethyl acetate, and dried under vacuum.…”

“…In continuation of our previous studies on novel curcuminoids (CUR) and CUR–BF 2 adducts, and with the recent discovery of demethylation as an additional metabolic pathway in parent curcumin, we synthesized two libraries of deuterated CUR–BF 2 and CUR compounds, one bearing OCD 3 groups (Figure ), and the other bearing halogenated phenyl rings and OCD 3 groups (Figure ), as models that may exhibit improved metabolic stability via a secondary/remote deuterium isotope effect stemming from the demethylation pathway. The ring‐deuterated hexamethoxy‐CUR–BF 2 and CUR compounds were also synthesized for comparison with their non‐deuterated analogues.…”

A Flexible Strategy for Modular Synthesis of Curcuminoid‐BF2/Curcuminoid Pairs and Their Comparative Antiproliferative Activity in Human Cancer Cell Lines

“…In previous studies aimed at synthesis of fluorinated CURs we showed the direct fluoro‐functionalization at the keto‐enolic position to prepare the α‐mono‐ and the gem‐difluoro derivatives . The forward synthesis as outlined above in Scheme does not permit the synthesis of the α‐carbonyl‐fluorinated CUR‐BF 2 adducts, or access to α‐methyl or methoxy‐substituted analogs, requiring previous access to the starting α‐substituted‐AA‐BF 2 adducts which is not straightforward.…”