Synthesis of novel psoralen analogues and their in vitro antitumor activity

Abstract

New tetracyclic benzofurocoumarin (benzopsoralen) analogues were synthesized and their inhibitory effect on the growth of tumor cell lines was evaluated. The human tumor cell lines used were MDA MB231 (breast adenocarcinoma), HeLa (cervix adenocarcinoma) and TCC-SUP (bladder transitional cell carcinoma). The in vitro antitumor activity of the new benzopsoralens was discussed in terms of structure-activity relationship. Molecular docking studies with human-CYP2A6 enzymes were also carried out with the synthesized compounds in order to evaluate the potential of these compounds to interact with the heme group of the enzymes. The results have demonstrated that the linear compounds have the most pronounced activity against tumor cell lines and this might be related to the better accessibility that these compounds have to the active site in relation to the angular ones that have shown in the majority of the cases multiple binding poses in the active site of CYP2A6.

Novel benzopsoralen analogues: Synthesis, biological activity and molecular docking studies

“…Furthermore, the compound 4 showed better activity for the MDA MB231 cell line than compounds 3 and 5, although for the TCC-SUP cell line it gave values on the same range as the compounds 3 and 5. The results herein obtained are in agreement with our previous studies using benzopsoralen analogues [4,5].…”

“…Therefore, it is an adequate model for molecular docking studies of the compounds herein synthesized. Previously, we reported that these compounds interact very closely with the iron ion of the haem group of the enzyme [4,5]. Ye and Zhang [16] demonstrated that the depletion of iron (haem deficiency) caused the apoptosis of HeLa cells, which involved the release of cytochrome c and the activation of caspase 3 (involved in the programmed cell death).…”

“…Additionally, Psoralen and 8-methoxypsoralen (8-MOP, named Xanthotoxin) are used for the treatment of Psoriasis in combination with UVA irradiation (PUVA therapy) [3]. It is important to notice that these compounds have also been reported to have an anti-cancer effect independently of its photoactivation [4,5]. It has been reported that Bergapten (5-methoxypsoralen) enhances p53 gene expression and induces apoptosis in human breast cancer cells [6].…”

“…Earlier in our group Psoralen derivatives were synthesized and their anti-proliferative effects on different human tumour cell lines were demonstrated [4,5]. The molecular docking results of these compounds with the CYP2A6 enzyme showed that, in general, the compounds carrying few bulky groups attached to the coumarin moiety adopted a conformation that allows the carbonyl group of the coumarin moiety to interact very closely with the iron ion of the haem cluster.…”

Oxidant‐Controlled Catalytic Transformations of Phenols with Unexpected Cleavage of Aromatic Rings

“…As shown in Scheme 4, the tert-butyl and methyl groupso f4a were easily removed by AlCl 3 in refluxing toluene, affording dibenzofuran-2-ol 7 in 91 %y ield. Compound 7 is an important intermediate for the synthesis of many bioactive substances, such as HeLa (cervix adenocarcinoma) and TCC-SUP (bladder transitional cell carcinoma) cells inhibitor 8, [20] HeLa and MDA MB231 (breasta denocarcinoma) cells inhibitor 9, [21] and H37Rv (mycobacterium tuberculosis) growth inhibitor 10. [22] In summary,an ovel coppercatalyzed tandemo xidative homocoupling/skeletal rearrangement of phenolst hat involves the cleavage of ab enzene ring under mild reaction conditions has been realized by using air or Ag 2 CO 3 as the oxidant.…”