Cyclotides are plant-derived mini-proteins of 28 - 37 amino acids. They have a characteristic head-to-tail cyclic backbone and three disulfide cross-linkages formed by six highly conserved cysteine residues, creating a unique knotted ring structure, known as a cyclic cystine knot (CCK) motif. The CCK topology confers immense stability to cyclotides with resistance to thermal and enzymatic degradation. Native cyclotides are of interest due to their multiple biological activities with several potential applications in agricultural (e.g. biopesticides, antifungal) and pharmaceutical (e.g. anti-HIV, cytotoxic to tumor cells) sectors. The most recent application of insecticidal activity of cyclotides is the commercially available biopesticidal spray known as 'Sero X' for cotton crops. Cyclotides have a general mode of action and their potency of bioactivity is determined through their binding ability, pore formation and disruption of the target biological membranes. Keeping in view the important potential applications of biological activities of cyclotides and the lack of an extensive and analytical compilation of bioactive cyclotides, the present review systematically describes eight major biological activities of the native cyclotides from four angiosperm families viz. Fabaceae, Poaceae, Rubiaceae, Violaceae. The bioactivities of 94 cytotoxic, 57 antibacterial, 44 hemolytic, 25 antifungal, 21 anti-HIV, 20 nematocidal, 10 insecticidal and 5 molluscicidal cyclotides have been comprehensively elaborated. Further, their distribution in angiosperm families, mode of action and future prospects have also been discussed.
Keywords: Antimicrobial; Cytotoxicity; Hemolytic; Insecticidal; Native cyclotides; Nematocidal.
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