[en] We describe herein the synthesis, characterization and biological studies of novel PEGylated triarylmethanes. Non-symmetrical and symmetrical triarylmethanes series have been synthesized by Friedel-Crafts hydroxyalkylation or directly from bisacodyl respectively followed by a functionalization with PEG fragments in order to increase bioavailability and biological effectiveness. The antimicrobial activity was investigated against Gram-positive and Gram-negative foodborne pathogens and against Candida albicans, an opportunistic pathogenic yeast. The biocidal activity was also studied using Staphylococcus aureus as a reference bacterium. Almost all PEGylated molecules displayed an antifungal activity comparable with fusidic acid with MIC values ranging from 6.25 to 50 μg/mL. Compounds also revealed a promising anti-biofilm activity with biofilm eradication percentages values above 80% for the best molecules (compounds 4d and 7). Compounds 7 and 8b showed a modest antiproliferative activity against human colorectal cancer cell lines HT-29. Finally, in silico predictions suggested adequate ADME and drug-likeness profiles for the synthetized triarylmethanes.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Ricco, Christophe; Conservatoire national des arts et métiers > Equipe de Chimie Moléculaire du Laboratoire Génomique, Bioinformatique et Chimie Moléculaire
Abdmouleh, Fatma; Conservatoire national des arts et métiers
Riccobono, Charlotte; Conservatoire national des arts et métiers
Guenineche, Lena; Conservatoire national des arts et métiers
Martin, Frederique; Université de Limoges
Goya-Jorge, Elizabeth ; Université de Liège - ULiège > Département de sciences des denrées alimentaires (DDA) > Gestion de la qualité dans la chaîne alimentaire
Liagre, Bertrand; Université de Limoges
Ben Ali, Mamdouh; Université de Sfax
Ferroud, Clotilde; Conservatoire national des arts et métiers
EL Arbi, Mehdi; Université de Sfax
Sylla-Iyarreta Veitía, Maité; Conservatoire national des arts et métiers > Equipe de Chimie Moléculaire du Laboratoire Génomique, Bioinformatique et Chimie Moléculaire
Language :
English
Title :
Pegylated triarylmethanes: Synthesis, antimicrobial activity, anti-proliferative behavior and in silico studies
Kirk, R.E., Othmer, D.F., Encyclopedia of Chemical Technology, Copper Alloys to Distillation. 1979, Wiley-Interscience.
Rose, E.R.A., Turner, F.M., The condensed chemical dictionary. 1961, Reinhold Publishing Corporation, New York.
G. Vijay Nair, S. Thomas, K. Abhilash, C. Smitha, Recent advances in the chemistry of triaryl-and triheteroarylmethanes (2006).
Culp, S.J., Beland, F.A., Malachite green: a toxicological review. J. Am. College Toxicol. 15 (1996), 219–238.
Nambo, M., Kurihara, D., Yamada, T., Nishiwaki-Ohkawa, T., Kadofusa, N., Kimata, Y., Kuwata, K., Umeda, M., Ueda, M., Combination of synthetic chemistry and live-cell imaging identified a rapid cell division inhibitor in tobacco and arabidopsis thaliana. Plant Cell Physiol. 57 (2016), 2255–2268.
Palchaudhuri, R., Nesterenko, V., Hergenrother, P.J., The complex role of the triphenylmethyl motif in anticancer compounds. J. Am. Chem. Soc. 130 (2008), 10274–10281.
J.L. Arbiser, Triarylmethane analogs and their use in treating cancers, in, vol. 10376522/ WO2009088838A2, 2009, pp. 64.
Panda, G., Shagufta, J.K., Mishra, V., Chaturvedi, A.K., Srivastava, R., Srivastava, B.S., Srivastava, diaryloxy methano phenanthrenes: a new class of antituberculosis agents. Bioorg. Med. Chem. 12 (2004), 5269–5276.
Panda, G., Parai, M.K., Srivastava, A.K., Chaturvedi, V., Manju, Y.K., Sinha, S., Design, synthesis and antitubercular activity of compounds containing aryl and heteroaryl groups with alkylaminoethyl chains. Indian J. Chem., Sect. B 48B (2009), 1121–1127.
Douglas, J.L., Panis, M.L., Ho, E., Lin, K.-Y., Krawczyk, S.H., Grant, D.M., Cai, R., Swaminathan, S., Cihlar, T., Inhibition of respiratory syncytial virus fusion by the small molecule VP-14637 via specific interactions with F protein. J. Virol. 77 (2003), 5054–5064.
Douglas, J.L., Panis, M.L., Ho, E., Lin, K.-Y., Krawczyk, S.H., Grant, D.M., Cai, R., Swaminathan, S., Chen, X., Cihlar, T., Small molecules VP-14637 and JNJ-2408068 inhibit respiratory syncytial virus fusion by similar mechanisms. Antimicrob. Agents Chemother. 49 (2005), 2460–2466.
Maité Sylla-Iyarreta, V., Dany Siverio, M., Vanessa, L., Marta, M., Rosa, M.G., Liliana Vicet, M., Yankier Rivero, G., Françoise, D., Clotilde, F., Peter, A.M.D.W., Alexander, D.C., Vicente, J.A., Yovani Marrero, P., Fishing Anti-Inflammatories from Known Drugs. In Silico Repurposing, Design, Synthesis and Biological Evaluation of Bisacodyl Analogues. Curr. Top. Med. Chem. 17 (2017), 2866–2887.
Kowaltowski, A.J., Turin, J., Indig, G.L., Vercesi, A.E., Mitochondrial effects of triarylmethane dyes. J. Bioenerg. Biomembr. 31 (1999), 581–590.
Wainwright, M., Burrow, S.M., Guinot, S.G., Phoenix, D.A., Waring, J., Uptake and cell-killing activities of a series of Victoria blue derivatives in a mouse mammary tumour cell line. Cytotechnology 29 (1999), 35–43.
Indig, G.L., Anderson, G.S., Nichols, M.G., Bartlett, J.A., Mellon, W.S., Sieber, F., Effect of molecular structure on the performance of triarylmethane dyes as therapeutic agents for photochemical purging of autologous bone marrow grafts from residual tumor cells. J. Pharm. Sci. 89 (2000), 88–99.
F. Guerin, V. Nicou, M. Nieto, Dyeing composition at acidic pH comprising a direct dye of triarylmethane structure, in, L'Oreal, Fr. WO2017108830A1, 2017, pp. 83.
D. Seneca, B. Boche, Hair cosmetic water-in-oil emulsions comprising triarylmethane direct dyes, in, L'Oreal, Fr. FR3059547A1, 2018, pp.76.
Görmen, M., Veitía, M.S.-I., Trigui, F., El Arbi, M., Ferroud, C., Ferrocenyl analogues of bisacodyl: Synthesis and antimicrobial activity. J. Organomet. Chem. 794 (2015), 274–281.
Li, W., Zhan, P., De Clercq, E., Lou, H., Liu, X., Current drug research on PEGylation with small molecular agents. Prog. Polym. Sci. 38 (2013), 421–444.
Thakur, A., Ranote, S., Kumar, D., Bhardwaj, K.K., Gupta, R., Chauhan, G.S., Synthesis of a PEGylated Dopamine ester with enhanced antibacterial and antifungal activity. ACS Omega 3 (2018), 7925–7933.
Mishra, P., Nayak, B., Dey, R., PEGylation in anti-cancer therapy: an overview. Asian J. Pharm. Sci. 11 (2016), 337–348.
Park, B.Y., Montgomery, T.P., Garza, V.J., Krische, M.J., Ruthenium catalyzed hydrohydroxyalkylation of isoprene with heteroaromatic secondary alcohols: Isolation and reversible formation of the putative metallacycle intermediate. J. Am. Chem. Soc. 135 (2013), 16320–16323.
O'Neill, A.J., Chopra, I., Preclinical evaluation of novel antibacterial agents by microbiological and molecular techniques. Expert Opin. Invest. Drugs 13 (2004), 1045–1063.
Seto, M., Aramaki, Y., Okawa, T., Miyamoto, N., Aikawa, K., Kanzaki, N., Niwa, S.-I., Iizawa, Y., Baba, M., Shiraishi, M., Orally active CCR5 antagonists as anti-HIV-1 agents: synthesis and biological activity of 1-benzothiepine 1, 1-dioxide and 1-benzazepine derivatives containing a tertiary amine moiety. Chem. Pharm. Bull. 52 (2004), 577–590.
Alexander, R., Warrellow, G., Eaton, M., Boyd, E., Head, J., Porter, J., Brown, J., Reuberson, J., Hutchinson, B., Turner, P., CDP840. A prototype of a novel class of orally active anti-inflammatory phosphodiesterase 4 inhibitors. Bioorg. Med. Chem. Lett. 12 (2002), 1451–1456.
Guay, D., Hamel, P., Blouin, M., Brideau, C., Chan, C.C., Chauret, N., Ducharme, Y., Huang, Z., Girard, M., Jones, T.R., Discovery of L-791,943: a potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor. Bioorg. Med. Chem. Lett. 12 (2002), 1457–1461.
Haginoya, N., Kobayashi, S., Komoriya, S., Yoshino, T., Nagata, T., Hirokawa, Y., Nagahara, T., Design, synthesis, and biological activity of non-amidine factor Xa inhibitors containing pyridine N-oxide and 2-carbamoylthiazole units. Bioorg. Med. Chem. 12 (2004), 5579–5586.
Nagendra Prasad, H.S., Manukumar, H.M., Karthik, C.S., Mallesha, L., Mallu, P., A novel copper (II) PAmPiCaT complex (cPAmPiCaTc) as a biologically potent candidate: a contraption evidence against methicillin-resistant Staphylococcus aureus (MRSA) and a molecular docking proof. Bioorg. Med. Chem. 27 (2019), 841–850.
Durcik, M., Tammela, P., Barančoková, M., Tomašič, T., Ilaš, J., Kikelj, D., Zidar, N., Synthesis and evaluation of N-phenylpyrrolamides as DNA gyrase B inhibitors. ChemMedChem 13 (2018), 186–198.
Desai, J., Liu, Y.-L., Wei, H., Liu, W., Ko, T.-P., Guo, R.-T., Oldfield, E., Structure, function, and inhibition of staphylococcus aureus heptaprenyl diphosphate synthase. ChemMedChem 11 (2016), 1915–1923.
Schweitzer, B.I., Dicker, A.P., Bertino, J.R., Dihydrofolate reductase as a therapeutic target. FASEB J. 4 (1990), 2441–2452.
Tihomir, T., Lucija Peterlin, M., Prospects for developing new antibacterials targeting bacterial type IIA topoisomerases. Curr. Top. Med. Chem. 14 (2014), 130–151.
Leung, S.S., Mijalkovic, J., Borrelli, K., Jacobson, M.P., Testing physical models of passive membrane permeation. J. Chem. Inf. Model. 52 (2012), 1621–1636.
Leung, S.S., Sindhikara, D., Jacobson, M.P., Simple predictive models of passive membrane permeability incorporating size-dependent membrane-water partition. J. Chem. Inf. Model. 56 (2016), 924–929.
Padmavathi, A.R., Pandian, S.K., Antibiofilm activity of biosurfactant producing coral associated bacteria isolated from gulf of mannar. Indian J. Microbiol. 54 (2014), 376–382.
Abdelli, F., Jardak, M., Elloumi, J., Stien, D., Cherif, S., Mnif, S., Aifa, S., Antibacterial, anti-adherent and cytotoxic activities of surfactin(s) from a lipolytic strain Bacillus safensis F4. Biodegradation 30 (2019), 287–300.
Cheng, L., Weir, M.D., Xu, H.H., Antonucci, J.M., Lin, N.J., Lin-Gibson, S., Xu, S.M., Zhou, X., Effect of amorphous calcium phosphate and silver nanocomposites on dental plaque microcosm biofilms. J. Biomed. Mater. Res. Part B: Appl. Biomater. 100:5 (2012), 1378–1386.
Bretin, L., Pinon, A., Bouramtane, S., Ouk, C., Richard, L., Perrin, M.-L., Chaunavel, A., Carrion, C., Bregier, F., Sol, V., Photodynamic therapy activity of new porphyrin-xylan-coated silica nanoparticles in human colorectal cancer. Cancers, 11, 2019, 1474.
Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., Bourne, P.E., The protein data bank. Nucl. Acids Res. 28 (2000), 235–242.
Pettersen, E.F., Goddard, T.D., Huang, C.C., Couch, G.S., Greenblatt, D.M., Meng, E.C., Ferrin, T.E., UCSF Chimera—A visualization system for exploratory research and analysis. J. Comput. Chem. 25 (2004), 1605–1612.
Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., Olson, A.J., AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J. Comput. Chem. 30 (2009), 2785–2791.
Wolber, G., Langer, T., LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. J. Chem. Inf. Model. 45 (2005), 160–169.
Trott, O., Olson, A.J., AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31 (2010), 455–461.
Schneider, N., Lange, G., Hindle, S., Klein, R., Rarey, M., A consistent description of hydrogen bond and dehydration energies in protein–ligand complexes: methods behind the HYDE scoring function. J. Comput. Aided Mol. Des. 27 (2013), 15–29.
SeeSAR version 9.2; BioSolveIT GmbH, Sankt Augustin, Germany, 2019, www.biosolveit.de/SeeSAR, s. d., in.
