Synthesis and biological evaluation of new nanosized aromatic polyamides containing amido- and sulfonamidopyrimidines pendant structures

Springer Science and Business Media LLC - Tập 9 - Trang 1-23 - 2015
Hammed H A M Hassan1, Elsayed M E Mansour1, Asmaa M S Abou Zeid1, Ehab R El-Helow2, Amel F Elhusseiny1, Raafat Soliman3
1Department of Chemistry, Faculty of Science, Alexandria University, Alexandria, Egypt
2Department of Microbiology and Immunology, Faculty of Pharmacy, Pharos University, Alexandria, Egypt
3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt

Tóm tắt

Antibiotics are biocides or products that inhibit the growth of microorganisms in the living cells and there are extensive works directed to develop efficient antimicrobial agents. The sulfonamide-containing polymers have great potential to resist gram-positive or gram-negative bacterial and fungal attacks. As a therapeutic agent, the sulfonamides have been reported as antitumor and antimicrobial agents against bacteria, being more potent against gram positive rather than gram negative strains. Design of new classes of inhibitors bearing fluorescent tails, as therapeutic and imaging agents, is currently an active area of research. Here, we describe the synthesis of a new family of polyamides based on chlorophenyl-3,5-diaminobenzamides, methyl substituted pyrimidinoamido-3,5-diamino- benzamides and methyl substituted pyrimidinosulfonamido-3,5-diaminobenzamides and evaluation of their thermal, optical and antimicrobial properties. We report the synthesis of a new series of nanosized polyamides containing bioactive pendent structures. The spherical nanosized polymer particles are soluble in many organic solvents and exhibited emissions ranging from blue to orange wavelength depending on the nature of the signaling unit. Pyrimidine- and p-chloroaromatic containing polymers exhibited higher bioactivity than that contain the sulfonamide group. The amidopyrimidine polymers exhibited remarkable antifungal and antibacterial activity and thus, these types of polymers are promising candidates for biomedical applications. The SEM analysis indicated that most of the polyamides were organized as well defined nano sized spheres, but in certain derivatives small amount of aggregated nanospheres were also observed. Thermal analyses were studied up to 700 °C and results showed comparable thermal behavior. The optical results revealed that polymeric series (A) exhibited orange emission, series (B) showed green emission while series (C) exhibited yellow and blue emissions. Benzene/pyridine structure interchange resulted in red shifted peaks attributed to the localized lone pair of electrons on a nitrogen atom which offer a greater electron affinity and better electron-transporting properties. The amido- and sulfonamide pyrimidine containing polymers exhibited the most potent antimicrobial activity. Relative to the reference Gentamicin, the polymer 54 exhibited comparable antibacterial activity against gram negative bacteria. Analogues 52 and 57 exhibited remarkable antibacterial activities compared to the references used. Thus, these polyamides are likely to be promising broad spectrum antibacterial agents and deserve further investigation at the molecular level.

Tài liệu tham khảo

Duncan R (2003) Polymer–drug conjugates. In: Budman D, Calvert H, Rowinsky E (eds) Handbook of anticancer drug development, vol 2. Lippincott Williams & Wilkins, Baltimore, pp 239–260 Al-Shamkhani A, Duncan R (1995) Synthesis, controlled release properties and antitumour activity of alginate-cis-aconityl-daunomycin conjugates. Int J Pharm 122:107–119 Coessens V, Schacht E, Domurado D (1996) Synthesis of polyglutamine and dextran conjugates of streptomycin with an acid-sensitive drug-carrier linkage. J Control Release 38:141–150 Rodrigues PCA, Scheuermann K, Stockmar C, Maier G, Fiebig HH, Unger C et al (2003) Synthesis and in vitro efficacy of acid-sensitive poly(ethylene glycol) paclitaxel conjugates. Bioorg Med Chem Lett 13:355–360 Munoz-Bonilla A, Fernández-García M (2012) Polymeric materials with antimicrobial activity. Progr Polym Sci 37:281–339 Lin J, Winkelmann C, Worley SD, Kim J, Wei CI, Cho U et al (2002) Biocidal polyester. J Appl Polym Sci 85:177–182 Ren X, Kocer HB, Kou L, Worley SD, Broughton RM, Tzou YM et al (2008) Antimicrobial polyester. J Appl Polym Sci 109:2756–2761 Hong KH, Sun G (2008) Poly(styrene-co-vinylbenzophenone) as photoactive antimicrobial and self-decontaminating materials. J Appl Polym Sci 109:3173–3179 Zhuo L, Kou K, Wang Y, Chen H (2015) Synthesis and characterization of pyrimidine-containing hyperbranched polyimides. Design Monomers Polym 18:42–45 Wang Y (2015) Synthesis and characterization of novel pyrimidine-containing poly (arylene ether)s. High Perform Polymers 27:59–64 Kumbar SG, Laurencein CT, Deng M (eds) (2014) Natural and synthetic biomedical polymers. Elsevier, San Diego Gunathilake SS, Magurudeniya HD, Huang P, Nguyen H, Rainbolt EA, Stefan MC et al (2013) Synthesis and characterization of novel semiconducting polymers containing pyrimidine. Polym Chem 4:5216–5219 Abd El-Rehim HA, El-Hag Ali A, Mostafa TB, Farrag HA (2004) Antimicrobial activity of anhydride copolymers and their derivatives prepared by ionizing radiation. Eur Polym J 40:2203–2212 Supuran CT, Innocenti A, Mastrolorenzo A, Scozzafava A (2004) Antiviral sulfonamide derivatives. Mini Rev Med Chem 4:189–200 Abbate F, Casini A, Owa T, Scozzafava A, Supuran CT (2004) Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isozymes I and II, and transmembrane, tumor-associated isozyme IX. Bioorg Med Chem Lett 14:217–223 Ghorab MM, Noaman E, Ismail MM, Heiba HI, Ammar YA, Sayed MY (2006) Novel antitumor and radioprotective sulfonamides containing pyrrolo [2,3-d]pyrimidines. Arzneimittelforschung 56:405–413 Ismail MM, Ghorab MM, Noaman E, Ammar YA, Heiba HI, Sayed MY (2006) Novel synthesis of pyrrolo [2,3-d] pyrimidines bearing sulfonamide moieties as potential antitumor and radioprotective agents. Arzneimittelforschung 56:301–308 Rostom SA (2006) Synthesis and in vitro antitumor evaluation of some indeno[1,2-c]pyrazol(in)es substituted with sulfonamide, sulfonylurea(-thiourea) pharmacophores, and some derived thiazole ring systems. Bioorg Med Chem 14:6475–6485 Ghosh AK, Chapsal BD, Weber IT, Mitsuya H (2008) Design of HIV protease inhibitors targeting protein backbone: an effective strategy for combating drug resistance. Acc Chem Res 41:78–86 Zhao ZJ, Wolkenberg SE, Lu MQ, Munshi V, Moyer G, Feng MZ et al (2008) Novel indole-3-sulfonamides as potent HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs). Bioorg Med Chem Lett 18:554–559 Lu RJ, Tucker JA, Pickens J, Ma YA, Zinevitch T, Kirichenko O et al (2009) Heterobiaryl human immunodeficiency virus entry inhibitors. J Med Chem 52:4481–4487 Chen H, Li H, Pei S, Wen X, Zhang Y (2009) Synthesis and characterization of fluoropoly(amide–sulfonamide)s via polycondensation. Polymer 50:4317–4324 Hassan HHAM, Elhusseiny AF, Sweyllam AM (2010) Synthesis of novel semiconducting aromatic polyesteramides containing pyridine: characterization of nanometer-sized rod-like analogues and their copper(II) complexes. J Macromol Sci Part A 47:521–533 Hassan HHAM, Elhusseiny AF, Sweyllam AM (2011) Synthesis and properties of narrow-sized spherical aramides nanoparticles containing pyridine and their copper(II) complexes. J Macromol Sci Part A 48:73–89 Hassan HHAM, Elhusseiny AF, Sweyllam AM (2011) Polyamides nanoparticles containing flexible linkages and their copper complexes with novel dielectric properties: structure-property relationship. J Mol Str 1001:89–103 Hassan HHAM, Elhusseiny AF, Sweyllam AM, Linhardt RJ (2013) Synthesis, dc-electrical conductivity and dielectric loss study of new type of narrow-sized spherical sulfonated aramides nanoparticles and their copper complexes. J Appl Polym Sci 128:310–321 Hassan HHAM, El-Banna SG, Elhusseiny AF, Mansour EME (2012) Synthesis of novel types of aramides nanoparticles with redox-active N-phthaloyl valine moieties and studying of their activity as antioxidants in the hepatic cytochrome P450 system in male rats. Molecules 17:8255–8275 Hassan HHAM, Elhusseiny AF, Elkony YMA, Mansour EME (2013) Synthesis, characterization and photoluminescence study of aromatic polyamides and poly(1,3,4-oxadiazole-amide)s nanoparticles containing pendent acetoxy bezamides groups. Chem Cent J 7:13 Elhusseiny AF, Hassan HHAM (2013) Antimicrobial and antitumor activity of platinum and palladium complexes of novel aramides nanoparticles containing flexibilizing linkages: structure-property relationship. Spectrochim Acta A 103:232–245 Zhang H (2004) Fire-safe polymers and polymer composites. In: National technical information service. Spring field, Virginia, pp 1–209 Van Krevelen DW, Hoftyzer PJ (1961) Properties of Polymers, third edn, Elsevier Scientific Publishing, pp 1 Horowitz HH, Metzger G (1963) A new analysis of thermogravimetric traces. Anal Chem 35:1464–1468 Lince F, Marchisio DL, Barresi AA (2008) Strategies to control the particle size distribution of poly-caprolactone nanoparticles for pharmaceutical application. J Colloid Interface Sci 322:505–515 Dhar ML, Singh O (1991) Kinetics and thermal decomposition of Fe(III) and UO2(II) complexes with embelin (2,5-dihydroxy-3-undecyl-P-benzoquinone). J Therm Anal 37:259–265 Traore K (1972) Analyse thermique differentielle et cinetique de reaction III. Surface des pics d’analyse thermique differentielle et applications. J Therm Anal 4:135 Maris P (1995) Modes of action of disinfectants. Rev sci tech Off int Epiz 14:47–55 Park SJ, Mehrad B (2009) Innate immunity to Aspergillus species. Clin Micro Rev 22:535–551 Mathuram AJ, Mohanraj P, Mathews MS (2013) Rhino-orbital-cerebral infection by Syncephalastrum racemosusm. J association phys 61:339–340 Mesaros N, Nordmann P, Ple´siat P, Roussel-Delvallez M, Van Eldere J, Glupczynski Y et al (2007) Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium. Clin Micro Infect 13:560–578