New Synthesis of Benzo-δ-carbolines, Cryptolepines, and Their Salts: In Vitro Cytotoxic, Antiplasmodial, and Antitrypanosomal Activities of δ-Carbolines, Benzo-δ-carbolines, and Cryptolepines

Abstract

The paper describes, in its first part, a new synthesis of benzo-delta-carbolines, cryptolepines, and their salts. The strategy is based on the association between halogen-dance and hetero-ring cross-coupling. It is fully convergent and regioselective with interesting overall yields from 27% to 70%. A halogen-dance mechanism in quinoline series is also proposed. The formal synthesis of potential antimalarial compounds and the first total synthesis of 11-isopropylcryptolepine are also described. In the second part, cytotoxic activity against mammalian cells and activities against Plasmodium falciparum and Trypanosoma cruzi of benzo-delta-carbolines and delta-carbolines were evaluated in vitro to study the structure-activity relationships. For benzo-delta-carbolines, methylation at N-5 increases the cytotoxic and antiparasitic activities. A further alkylation on C-11 generally increases the cytotoxic activity but not the antiparasitic activity, cryptolepine and 11-methylcryptolepine being the most active on both parasites. Taking advantage of the fluorescence of the indoloquinoline chromophore, cryptolepine was localized by fluorescence microscopy in parasite DNA-containing structures suggesting that these compounds act through interaction with parasite DNA as proposed for cryptolepine on melanoma cells. For delta-carbolines, methylation at N-1 is essential for the antimalarial activity. 1-Methyl-delta-carboline specifically accumulates in the intracellular parasite. It has weak cytotoxic activity and can be considered as a potential antimalarial compound.

Membrane Perturbations Induced by New Analogs of Neocryptolepine

“…This fact caused significant interest for the synthesis of indoloquinoline alkaloid derivatives, because of their potential biomedical and pharmaceutical value. 1,[17][18][19][20][21][22][23][24][25][26][27] Previous studies have indicated that all indolo[2,3-b]-quinolines belonging to the 5H-series possess interesting biological activities, including inhibition of the growth of Gram-positive bacteria and pathogenic fungi, cytotoxicity against KB cells and stimulation of the formation of calf thymus topoisomerase II mediated DNA cleavage. 17) 5,11-Dimethyl-5H-indolo [2,3-b] quinoline (DIMIQ), a benzoiso-α-carboline derivative, is one of the most interesting and active representatives of this group (Fig.…”

Small molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis

“…13 Other effects on cells and organs include modulating the extrinsic or death receptor pathway and the intrinsic or mitochondrial pathway, 14 interfering with Ras-related signaling pathways, 15 inhibiting tumor-related enzymes, [16][17][18][19] and limiting thrombosis and inflammation. [20][21][22] Inflammation is a wellrecognized and critical component of the tumor progression, 23,24 and thromboembolism is a leading cause of cancer patient death.…”

Synthesis of some novel 1,2,4-triazole derivatives as potential antimicrobial agents

“…On the other hand, quinoline derivatives have been proven as privileged core structures and confirmed in bioactive natural products and in various pharmaceutical agents. They are known for their antiplasmodial properties and have been used as the staring compounds for new antimalarial agents [25,26].…”