The present study concerns the identification of nine thus-far unknown derivatives of carminic acid extracted from pre-Columbian Peruvian textiles dyed with American cochineal—these derivatives are not found in commercially available preparations of the dye. These compounds probably represent a unique fingerprint of dyed textiles from this region, as they have never been reported to occur in other fabrics of historical value. They were separated by reversed-phase high-performance liquid chromatography (phenyl column) and detected using a UV/vis spectrophotometer and two tandem mass spectrometers. Peaks observed in chromatograms registered at 450 and 500 nm were further identified by ESI QqQ MS (mainly in the negative ion mode), supported by high-resolution ESI QIT/ToF MS data. The characteristic fragmentation pathways of isolated carminic acid and its derivatives provided additional information concerning lost neutrals and thus the functional groups and substituents present in the parent molecules. This information mainly related to multiple cleavages of the hexoside moiety (initially cross-ring cleavage), which are characteristic of C-glucosides (loss of 90, 120, and 148 Da). This is accompanied by the elimination of H2O as well as the further loss of 60 Da from the hexoside moiety. Moreover, other losses from the carbonyl groups (44 Da from CO2 loss, 62 Da from ethylene glycol loss, 32 Da from O2 loss, 138 Da from hydroxybenzoic acid, and 120 Da from oxomethylene cyclohexadienone) provided more specific information about structures of the identified derivatives of carminic acid.

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Neuropilin-1 has been found to be overexpressed in several kinds of malignant tumors, and it is postulated that its interaction with the vascular endothelial growth factor 165 leads to progression of tumor vascularization and growth. Several analogues (KxxR) with various conformational latitudes have been synthesized and found as inhibitors of NRP-1. Detailed insight provided by molecular dynamics simulation allowed forming a clear relationship between flexibility of xx part of the molecule and its inhibitory activity.

Inhibiting the interaction of neuropilin-1 (NRP-1) with vascular endothelial growth factor (VEGF) has become an interesting mechanism for potential anticancer therapies. In our previous works, we have obtained several submicromolar inhibitors of this interaction, including branched pentapeptides of general structure Lys(Har)-Xxx-Xxx-Arg. With the intent to improve the proteolytic stability of our inhibitors, we turned our attention to 1,4-disubstituted 1,2,3-triazoles as peptide bond isosteres. In the present contribution, we report the synthesis of 23 novel triazolopeptides along with their inhibitory activity. The compounds were synthesized using typical peptide chemistry methods, but with a conversion of amine into azide completely on solid support. The inhibitory activity of the synthesized derivatives spans from 9.2% to 58.1% at 10 μM concentration (the best compound Lys(Har)-GlyΨ[Trl]GlyΨ[Trl]Arg, 3, IC50 = 8.39 μM). Synthesized peptidotriazoles were tested for stability in human plasma and showed remarkable resistance toward proteolysis, with half-life times far exceeding 48 h. In vitro cell survival test resulted in no significant impact on bone marrow derived murine cells 32D viability. By means of molecular dynamics, we were able to propose a binding mode for compound 3 and discuss the observed structure–activity relationships.