Synthesis and Biological Evaluation of Indoloquinoline Alkaloids

Indoloquinoline alkaloids constitute a family of tetracyclic heterocycles combining an indole nucleus with a quinoline framework. These natural and nature-inspired molecules have attracted sustained interest owing to their diverse pharmacological profiles, notably anticancer, antimalarial and antimicrobial activities. Synthetic access to these scaffolds has been achieved through a range of strategies, including palladium-catalysed annulation of o-acylanilines, nucleophilic aromatic substitution approaches and Pictet–Spengler-type cyclisations. Such methods permit systematic functionalisation at key positions (for example C5, C11) and the assembly of hybrid architectures, such as artemisinin-indoloquinoline conjugates. Biological evaluation typically encompasses in vitro antiproliferative assays against carcinoma and leukaemia cell lines, mechanistic studies of DNA intercalation and topoisomerase II inhibition, and in vivo tumour models in rodents. Recent work has illuminated structure–activity relationships that govern potency and selectivity, revealing that planar heteroaromatic surfaces facilitate DNA binding while side-chain modifications modulate cellular uptake and off-target toxicity. Computational tools, including molecular docking and ADME profiling, now guide rational derivative design. Despite challenges in improving water solubility and reducing systemic toxicity, indoloquinoline alkaloids remain promising leads for the development of novel therapeutic agents with global significance.

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Synthesis and Biological Evaluation of Indoloquinoline Alkaloids publication trend

The graph below shows the total number of articles in synthesis and biological evaluation of indoloquinoline alkaloids across all publications each year (not limited to Nature Index journals).

Technical terms

IC50: The concentration of a compound required to inhibit a particular biological process by 50% under defined conditions.

ADME: An acronym for absorption, distribution, metabolism and excretion, describing the pharmacokinetic profile of a compound in a biological system.

Apoptosis: A regulated form of programmed cell death characterised by cellular shrinkage, chromatin condensation and caspase activation.

Molecular docking: A computational technique used to predict the preferred orientation and binding affinity of a small molecule when bound to a target macromolecule.

References

1. Cytotoxic Potential of Novel Quinoline Derivative: 11-(1,4-Bisaminopropylpiperazinyl)5-methyl-5H-indolo[2,3-b]quinoline against Different Cancer Cell Lines via Activation and Deactivation of the Expression of Some Proteins. International Journal of Molecular Sciences (2023).
2. Structural Modifications of Nature-Inspired Indoloquinolines: A Mini Review of Their Potential Antiproliferative Activity. Molecules (2019).
3. Design, Synthesis, and Biological Evaluation of Artemisinin-Indoloquinoline Hybrids as Potent Antiproliferative Agents. Molecules (2014).
4. In Vitro and In Vivo Antitumor Activity of Indolo[2,3-b] Quinolines, Natural Product Analogs from Neocryptolepine Alkaloid. Molecules (2021).
5. Synthesis and Evaluation of the Tetracyclic Ring-System of Isocryptolepine and Regioisomers for Antimalarial, Antiproliferative and Antimicrobial Activities. Molecules (2021).