Oxoisoaporphines and Aporphines: Versatile Molecules with Anticancer Effects.

Cancer is a disease that involves impaired genome stability with a high mortality index globally. Since its discovery, many have searched for effective treatment, assessing different molecules for their anticancer activity. One of the most studied sources for anticancer therapy is natural compounds and their derivates, like alkaloids, which are organic molecules containing nitrogen atoms in their structure. Among them, oxoisoaporphine and sampangine compounds are receiving increased attention due to their potential anticancer effects. Boldine has also been tested as an anticancer molecule. Boldine is the primary alkaloid extract from boldo, an endemic tree in Chile. These compounds and their derivatives have unique structural properties that potentially have an anticancer mechanism. Different studies showed that this molecule can target cancer cells through several mechanisms, including reactive oxygen species generation, DNA binding, and telomerase enzyme inhibition. In this review, we summarize the state-of-art research related to oxoisoaporphine, sampangine, and boldine, with emphasis on their structural characteristics and the relationship between structure, activity, methods of extraction or synthesis, and anticancer mechanism. With an effective cancer therapy still lacking, these three compounds are good candidates for new anticancer research.

Synthesis and Docking of Novel 3-Indolylpropyl Derivatives as New Polypharmacological Agents Displaying Affinity for 5-HT1A R/SERT.

A series of novel 3-indolylpropyl derivatives was synthesized and evaluated for their binding affinities at the serotonin-1A receptor subtype (5-HT1A R) and the 5-HT transporter (SERT). Compounds 11b and 14b exhibited the highest affinities at the 5-HT1A R (Ki = 43 and 56 nM), whereas compounds 11c and 14a were the most potent analogs at the SERT (Ki = 34 and 17 nM). On the other hand, compounds 14b and 11d showed potent activity at both targets, displaying a profile that makes them promising leads for the search for novel potent ligands with a dual mechanism of action. Molecular docking studies in all the compounds unveiled relevant drug-target interactions, which allowed rationalizing the observed affinities.

Synthesis, docking and pharmacological evaluation of novel homo- and hetero-bis 3-piperazinylpropylindole derivatives at SERT and 5-HT1A receptor.

A series of 3-(3-(4-(3-(1H-indol-3-yl)propyl)piperazin-1-yl)propyl)-1H-indole derivatives (3a-d and 5a-f) as homo- and hetero-bis-ligands, were synthesized and evaluated for in vitro affinity at the serotonin transporter (SERT) and the 5-HT1A receptor. Compounds 5b and 5f showed nanomolar affinities for both targets. The experimental data were rationalized according to results obtained from docking experiments. These findings are in agreement with our proposal that bis-indole derivatives can bind both targets, and might serve as leads in the quest of ligands endowed with a dual mechanism of action.