ediate could possibly be rationalized by initial epoxidation on the prenyl group at C-3. . Further reductive H2 Receptor Modulator Gene ID cleavage or hydrolysis in the epoxide intermediate led towards the at C-3 Additional reductive cleavage or hydrolysis in the epoxide intermediate led towards the generation of metabolites 17 or 18, respectively. In addition, O-methylation in the hydroxyl generation of metabolites 17 or 18, respectively. In addition, O-methylation in the hydroxyl groupat C-3 in 17 could kind 11. Meanwhile, aa spontaneous intramolecular attack in the group at C-3 in 17 could form 11. Meanwhile, spontaneous intramolecular attack of your neighboring oxygen atom at C-2 in 22 could bring about the metabolite 21. Hydrogenation neighboring oxygen atom at C-2 in 22 could result in the metabolite 21. Hydrogenation of with the ,-double bonds in 22, 17, 18, and 11 could generate their IL-17 Antagonist manufacturer corresponding hydrogenthe ,-double bonds in 22, 17, 18, and 11 could create their corresponding hydrogenated ated metabolites 16,20, and ten,ten, respectively. Metabolites16 and 19 could possibly be regarded metabolites 16, 19, 19, 20, and respectively. Metabolites 16 and 19 might be regarded as as intermediates to make as intermediates to produce the rest from the metabolites. Inside the case ofof 16, a spontaneous the rest from the metabolites. Inside the case 16, a spontaneous intramolecular attack from the neighboring oxygen atom at C-4 could outcome inside the opening intramolecular attack on the neighboring oxygen atom at C-4 could outcome within the opening of of epoxide ring to kind its respective metabolite 15. Inside the case of 19, similarly, intramoepoxide ring to form its respective metabolite 15. Inside the case of 19, similarly, intramolecular lecular cyclization of the prenyl group by the neighboring hydroxyl group at C-2 or C-4 cyclization of the prenyl group by the neighboring hydroxyl group at C-2 or C-4 could could form a 2,2-dimethyldihydropyran moiety in 14 (pathway b) or 13 (pathway a). Adform a two,2-dimethyldihydropyran moiety in 14 (pathway b) or 13 (pathway a). Moreover, ditionally, metabolite 12 could be formed by O-ethylation of the hydroxyl group at C-3 metabolite 12 might be formed by O-ethylation with the hydroxyl group at C-3 of 19. of 19.2.four. Cytotoxicity Evaluation 2.four. Cytotoxicity Evaluation The parent compounds 1 and all isolated metabolites 51 have been evaluated for The parent compounds 1 and all isolated metabolites 51 had been evaluated for in in vitro cytotoxic possible against human cancer cell lines A375P, HT-29, and MCF-7 utilizing vitro cytotoxic prospective against human cancer cell lines A375P, HT-29, and MCF-7 working with modified MTT system [29]. The outcomes are presented on Table four. Noteworthily, compounds 1 and 12 showed the strongest cytotoxic activities against human cancer cell lines A375P, A549, and MCF-7 with IC50 values ranging from four.4 to ten.1 , whilst compounds two and 4 have been moderately cytotoxic.Int. J. Mol. Sci. 2021, 22,9 ofTable four. Cytotoxic activities of compounds 1 and their metabolites 51 a . Compound 1 two three 4 five 6 7 8 9 10aIC50 SD ( ) A375P eight.09 0.35 25.48 1.53 one hundred 5.21 0.39 one hundred one hundred 100 29.41 1.86 100 14.20 0.40 29.38 0.59 HT-29 7.54 0.70 25.98 0.72 one hundred 21.34 1.40 one hundred one hundred 100 57.17 four.28 100 73.39 0.48 one hundred MCF-7 9.20 0.13 26.99 0.77 one hundred 20.94 0.19 100 one hundred one hundred 59.44 0.39 one hundred 47.23 1.07 61.75 1pound 12 13 14 15 16 17 18 19 20 21 DZIC50 SD ( ) A375P 4.35 0.35 27.38 0.67 31.90 1.27 66.57 1.91 28.91 1.99 42.98 0.62 70.05 1.27 21.92 two.26 57.60 0.67 one hundred two.10 0.06 HT-29 5.77 0.28 60.15 1.15 77.65 1.33 100 one hundred 100 100
