neocryptolepine and Neoplasms

Indoloquinoline (IQ) is an important class of naturally occurring antimalarial alkaloids, mainly represented by cryptolepine, isocryptolepine, and neocryptolepine. The IQ structural framework consists of four isomeric ring systems differing via the linkage of indole with quinoline as [3,2-b], [3,2-c], [2,3-c], and [2,3-b]. Structurally, IQs are planar and thus they bind strongly to the DNA which largely contributes to their biological properties. The structural rigidity and associated nonspecific cellular toxicity is a key shortcoming of the IQ structural framework for preclinical development. Thus, the lead optimization efforts were aimed at improving the therapeutic window and ADME properties of IQs. The structural modifications mainly involved attaching the basic aminoalkyl chains that positively modulates the vital physicochemical and topological parameters, thereby improves biological activity. Our analysis has found that the aminoalkylation consistently improved the selectivity index and provided acceptable in-vivo antimalarial/anticancer activity. Herein, we critically review the role of aminoalkylation in deciphering the antimalarial and cytotoxic activity of IQs.

Topics: Alkaloids; Antimalarials; Antineoplastic Agents; Cell Proliferation; Indoles; Malaria; Molecular Structure; Neoplasms; Quinolines

Indoles constitute extensively explored heterocyclic ring systems with wide range of applications in pathophysiological conditions that is, cancer, microbial and viral infections, inflammation, depression, migraine, emesis, hypertension, etc. Presence of indole nucleus in amino acid tryptophan makes it prominent in phytoconstituents such as perfumes, neurotransmitters, auxins (plant hormones), indole alkaloids etc. The interesting molecular architecture of indole makes them suitable candidates for the drug development. This review article provides an overview of the chemistry, biology, and toxicology of indoles focusing on their application as drugs. Our effort is to corroborate the information available on the natural indole alkaloids, indole based FDA approved drugs and clinical trial candidates having diverse therapeutic implementations. This compiled information may serve as a benchmark for the alteration of existing ligands to design novel potent molecules with lesser side effects.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antiemetics; Antineoplastic Agents; Bacterial Infections; Chemistry, Pharmaceutical; Cholinergic Antagonists; Drug Discovery; Humans; Indoles; Migraine Disorders; Mycoses; Neoplasms; Virus Diseases

The naturally occurring neocryptolepine (5-Methylindolo [2,3-

Topics: Alkaloids; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Delayed-Action Preparations; Drug Liberation; Humans; Hydrogen-Ion Concentration; Nanoparticles; Neoplasms; Quinolines; Silicon Dioxide