Naturally Occurring Calanolides: Occurrence, Biosynthesis, and Pharmacological Properties Including Therapeutic Potential

Abstract

Calanolides are tetracyclic 4-substituted dipyranocoumarins. Calanolide A, isolated from the leaves and twigs of Calophyllum lanigerum var. austrocoriaceum (Whitmore) P. F. Stevens, is the first member of this group of compounds with anti-HIV-1 activity mediated by reverse transcriptase inhibition. Calanolides are classified pharmacologically as non-nucleoside reverse transcriptase inhibitors (NNRTI). There are at least 15 naturally occurring calanolides distributed mainly within the genus Calophyllum, but some of them are also present in the genus Clausena. Besides significant anti-HIV properties, which have been exploited towards potential development of new NNRTIs for anti-HIV therapy, calanolides have also been found to possess anticancer, antimicrobial and antiparasitic potential. This review article provides a comprehensive update on all aspects of naturally occurring calanolides, including their chemistry, natural occurrence, biosynthesis, pharmacological and toxicological aspects including mechanism of action and structure activity relationships, pharmacokinetics, therapeutic potentials and available patents.

Comparative Antiseizure Analysis of Diverse Natural Coumarin Derivatives in Zebrafish

“…Oxypeucedanin (1), oxypeucedanin hydrate (2), and notopterol (3) decreased normalized PSD per larva to a similar level with 83-89%. Among the dihydrofuranocoumarins, nodakenin (13) decreased normalized PSD by 77%, while nodakenetin (12) only non-significantly reduced the PSD by 26%. Hence, while nodakenin was inactive in the locomotor assay, it has pronounced antiepileptiform activity, and the opposite is observed for nodakenetin, with antiseizure activity observed only after behavioral analysis.…”

“…In most cases (the exception here was daphnoretin), the MTC was the most effective concentration and the lowest concentration had the weakest protective effect. In the group of dihydrofuranocoumarins, nodakenetin (12) showed significant and concentration-dependent antiseizure activity at 100-400 µM, with activities ranging between 17 and 29%, while nodakenin (13), a glycoside of nodakenetin, was inactive. Hyuganin C (18), belonging to the dihydropyranocoumarin, showed significant protective properties at 10 and 20 µM, decreasing seizure-like behavior by 27 and 35%, respectively.…”

“…Methoxypsoralen derivatives are popularly used in PUVA (psoralen and ultraviolet A) therapy in the treatment of psoriasis and vitiligo. (+)-Calanolide A, a tetracyclic dipyranocoumarin, attracted attention as a potential anti-HIV agent with activity mediated by reverse transcriptase inhibition [ 11 , 12 ].…”

4-(Dimethylamino)pyridine as an Efficient Catalyst for One-Pot Synthesis of 1,4-Pyranonaphthoquinone Derivatives viaMicrowave-Assisted Sequential Three Component Reaction in Green Solvent

“…These derivatives possess a wide range of pharmacological activities, for example, anticancer, 10 antitumor, 11 leishmanicidal, 12 antibacterial, antifungal, 13 and cytotoxic. 14 On the other hand, chromenes, which are components of numerous naturally occurring products, like calanolides, 15,16 and calophyllolides, 17 have been "key" scaffolds associated with a wide range of pharmacological activities including anticancer, 18,19 anti-HIV, 20,21 antitumor, 22 antiproliferation, 23 antibacterial, 24 and antimalarial. 25,26 Moreover, a huge number of synthetic 2-amino-3-cyano-chromene derivatives possess potential biological activities, for example, compound 5 has exhibited antibacterial activity against Staphylococcus aureus, compounds 6, 7, and 8 have strong inhibitory activity against Epidermophyton floccosum, and compound 8 has exhibited activity against Aspergillus clavatus, Candida glabarata, C. dubliniensis, C. albicans, and C. tropicalis (Figure 1).…”

Coumarin and Its Derivatives—Editorial

“…These two natural products have been described for their anticancer, antidiabetic, antifertility, antimicrobial, antiplatelet aggregation, antiprotozoal, antiviral, and calcium antagonistic properties. The same group focused a second review on the natural origin, biosynthesis, and pharmacological activities of tetracyclic 4-substituted dipyranocoumarins, the calanolides [17]. Ultra-high-performance liquid chromatography coupled with a mass spectrometry (UHPLC-MS) methodology has been used for identifying and quantifying coumarins from a group of twenty-eight plants (roots and leaves) from Arabidopsis natural populations [18].…”