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The pomegranate (PMG; Punica granatum L.) fruit has an ideal nutritional/functional profile, with well-doccumented health benefits. Many of its antioxidant phytochemicals may exert antitumoral activities, though they natural occurrence/bioactivity may be affected by the plant varietal (cv). Here, the nutritional (spectrophotometry) and phenolic compounds (PC) profile (UPLC-DAD-MS2), total radical (ABTS) scavenging capacity (RSC), and antiproliferative activity [in vitro (MTT assay), in silico (ADMET, cheminformatics)] of three ripe pomegranate fruits [red (cv. Wonderful), pink (cv. Molar de Elche), white (cv. Indian) PMG], were evaluated. The contents [range (total) per-100 g DW] of ascorbic acid (~19-105 mg), tocols (tocopherols> tocotrienols; ~ 32-110 μg), carotenoids (lutein> α/β-carotene; ~21-32 μg), and phenolic compounds [total (~1.82-2.45 gGAE), flavonoids (~0.17-0.32 gQE), anthocyanins; (~0-8.07 gCy3GE)] were no-trend yet cv-specific. The RSC (µmolTE/g DW) was red (44.5)> pink (36.9)> white (19.6) as related to their PC richness (sixteen molecules identified). Four PC seemed to be highly bioaccesibile (GI tract) and bioavailable (systemic) [ellagic acid (pink), vanillic acid (red), gallic acid (white), D-(+)-catechin (white)], three of them having multiple protein targets (number) against cancer [ellagic acid (52) > vanillic acid (32) > gallic acid (23)], particularly exhibiting a strong inhibitory activity on several human carbonic anhydrases (hCA, metalloenzyme; E.C. EC 4.2.1.1; isoforms (I, II, II, IV, VB, VI, VII, IX, XII, XIV). Despite this evidence, the cytotoxic capacity of all three extracts in normal (retina) and cancerous (breast, lung, colorectal) cell lines was low (IC50 > 200 μg/mL) with no apparent cv-related effect. The anticancer potential of the assayed PMG extracts appears to be cv-specific (red> pink> white), although the effectiveness of red PMG (the most promising), could be more effective if concentrated into a nutraceutical formulation. Acknowledgements: Mexican Council of Science and Technology (Project: CB-2015-1/254063).
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