Cytotoxicity of Naturally Occurring Isoquinoline Alkaloids of Different Structural Types

Abstract

Forty-six isoquinoline alkaloids, of eleven structural types isolated in our laboratory, have been evaluated for their cytotoxicity against two cancer cell lines (Caco-2 and Hep-G2 cancer cells), as well as against normal human lung fibroblast cells. Only scoulerine, aromoline, berbamine and parfumidine showed significant cytotoxic effects, but only scoulerine was active against both Caco-2 and Hep-G2 cells (IC 50 values 6.44 + 0.87 and 4.57 + 0.42, respectively). Unfortunately, except for parfumidine, the other active alkaloids were also cytotoxic to the normal human lung fibroblast cells.

Scoulerine affects microtubule structure, inhibits proliferation, arrests cell cycle and thus culminates in the apoptotic death of cancer cells

“…In our previous study we reported that scoulerine has a potent antiproliferative activity against Caco-2 and Hep-G2 cancer cells 11 . Another recent work in this direction showed that scoulerine isolated from the stems of Xylopia laevigata was cytotoxic toward the tumor cell lines B16-F10, HepG2, K562 and HL-60 12 .…”

“…Scoulerine was found to be active as an inhibitor of ß-site amyloid precursor protein cleaving enzyme 1 (BACE1), which is a very promising target for the treatment of Alzheimer’s disease (AD) 5 . In our follow-up work, when considering forty-six isoquinoline alkaloids screened by MTT assay, scoulerine exhibited impressive cytostatic activity against gastrointestinal cancer cells 11 . Although our recent study demonstrated the bioactivity of scoulerine with an emphasis on the cytostatic action that may be of interest in cancer chemotherapy, further studies remain to be undertaken to better explore its anticancer potential.…”

In Vitro and In Silico Acetylcholinesterase Inhibitory Activity of Thalictricavine and Canadine and Their Predicted Penetration across the Blood-Brain Barrier

“…Additionally, to consider compounds potential anti-Alzheimer’s disease drugs, candidates do not have to possess any significant toxic effect. In a recent study by Chlebek et al, 1 and 2 were determined as non-cytototoxic (IC 50 values > 10 µM) against selected human carcinoma and non-carcinoma cells [39]. Furthermore, in vivo, it was found that tetrahydroprotoberberine alkaloids (e.g., (±)-form and (−)-form of 2 possess low acute toxicity, their LD 50 values in mice by oral administration were 940 and > 2000 mg/kg, respectively [40,41].…”

Can Isoquinoline Alkaloids Affect Platelet Aggregation in Whole Human Blood?

“…Another interesting aspect is the fact that many isoquinoline alkaloids also have cytostatic effects [ 1 , 13 , 14 , 15 ]. Tumors have been shown to promote platelet aggregation and trigger thrombotic episodes also known as tumor cell-induced platelet aggregation whilst platelets can promote cancer growth and metastasis [ 16 , 17 ].…”

“…Taking this discovered link between platelets and cancer into account, antiplatelet effects might be useful in cancer treatments. The published studies with isoquinoline alkaloids documented a variable potency (IC 50 ) against different cancer cell lines, ranging from 3 μM to almost inactive compounds [ 1 , 13 , 14 , 15 , 18 ]. Based on the aforementioned information, we decided to test the antiplatelet effects of a palette of 14 isoquinoline alkaloids ( Figure 1 ), 6 of which, as far as we know, have never been tested for their antiplatelet effects.…”