“SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITIES OF NOVEL DIHYDROXYBEZALDEHYDE DERIVATIVES OF 4-AMINOPYRROLO [2, 3-d] PYRIMIDINE”

Main Article Content

Umesh Nilkanth Pol

Keywords

2,6-dihydroxy benzaldehyde, 4-aminopyrrolo[2,3-d]pyrimidine, Antibacterial activity

Abstract

The main aims of this work were to prepare new pyrrolopyrimidine compounds, analyse their properties, and assess their effectiveness against bacteria and fungi. The objective of this study was to synthesise dihydroxybenzaldehyde derivatives of the pyrrolopyrimidine. The synthesised compounds were characterised using spectroscopic techniques. The synthesised compounds were evaluated for their antimicrobial efficacy against four bacterial strains and two yeast strains, namely, S. aureus MCC 2010, B. subtilis MCC 2010, E. coli MCC 2412, P. aeruginosa MCC 2080, C. albicans MCC 1439, and S. cerevisiae. Each of the synthesised compounds exhibited prominent peaks in FT(IR), 1H and 13C NMR, and UV spectral studies. The compound 2a was proven to have greater antibacterial and antifungal activity in vitro compared to the gold standards streptomycin and fluconazole.

Abstract 38 | pdf Downloads 23

References

C.T. Supuran, A. Scozzafava, B.C. Jurca, M.A. Iiies, Synthesis of substituted ureido and thioureido derivatives of aromatic/heterocyclic sulfonamides with increased affinities for isozyme I. European Journal of medicinal chemistry, Synthesis of substituted ureido and thiourea derivatives of aromatic/heterocyclic sulfonamides with increased affinities for isozyme I, Euro J of Med Chem. 33:2, (1998) 83-93. https://doi.org/10.1016/S0223-5234(98)80033-0
[2] G. Mangalagiu, M. Ungureanu, G. Grousu, I. Nangalagiu, M. Petrovanu, New pyrrolo-pyrimidine derivatives with antifungal or antibacterial properties in vitro Pharm. Fr. 59 (2001) 139-140.
[3] C.V. Varaprasad, K.S. Ramasamy, J.L. Girardet, E. Gunic, V. Lai, W. Zhong, H. An, Z. Hong, Synthesis of new pyrrolo[2,3-d]pyrimidine derivatives as antibacterial and antifungal agents, Chem. Pharm. Bull. 56 (2008) 1617. https://doi.org/10.1016/j.ejmech.2010.08.043.
[4] C.V. Varaprasad, K.S. Ramasamy, J.L. Girardet, E. Gunic, V. Lai, W. Zhong, H. An, Z. Hong, Synthesis of pyrrolo[2,3-d]pyrimidine nucleoside derivatives as potential anti-HCV agents, Bioorg. Chem. 35 (2007) 25-34. https://doi.org/10.1016/j.bioorg.2006.07.003.
[5] M.A. Ivanov, A.V. Ivanov, I.A. Krasnitskaya, O.A. Smirnova, I.L. Karpenko, E.F. Belanov, V.S. Prasolov, V.L. Tunitskaya, L.A. Alexandrova, New furano- and pyrrolo[2,3-d]pyrimidine nucleosides and their 5′-O-triphosphates: Synthesis and biological properties, Russ. J. Bioorg. Chem. 34 (2008) 593–601. https://doi.org/10.1134/S1068162008050099.
[6] M.S. Mohamed, A.E. Rashad, M. Adbel-Monem, S.S. Fatahalla, Z. Naturforsch C; New Anti-Inflammatory Agents, Zeitschrift für Naturforschung C. 62 (2007) 27-31. https://doi.org/10.1515/znc-2007-1-205.
[7] S. Nagashima, T. Hondo, H. Nagata, T. Ogiyama, J. Maeda, H. Hoshii, T. Kontani, S. Kuromitsu, K. Ohga, M. Orita, K. Ohno, A. Moritomo, K. Shiozuka, M. Furutani, M. Takeuchi, M. Ohta, S. Tsukamoto, Novel 7H-pyrrolo [2, 3-d] pyrimidine derivatives as potent and orally active STAT6 inhibitors, Bioorg. Med. Chem. 17(2009) 6926-6936. https://doi.org/10.1016/j.bmc.2009.08.021.
[8] B.A. Harrison, N.A. Whitlock, M.V. Voronkov, Z.Y. Almstead, K.J. Gu, R. Mabon, M. Gardyan, B.D. Hamman, J. Allen, S. Gopinathan, B. McKnight, M. Crist, Y. Zhang, Y. Liu, L.F. Courtney, B. Key, J. Zhou, N. Patel, P.W. Yates, Q. Liu, A.G. Wilson, S.D. Kimball, C.E. Crosson, D.S. Rice, D.B. Rawlins, iscovery of bis-aryl urea derivatives as potent and selective Limk inhibitors, J. Med. Chem. 52(2009) 7464-7477. https://doi.org/10.1016/j.bmc.2015.10.041.
[9] S.I. Alqasoumi, M.M. Ghorab, Z.H. Ismail, S.M. Abdel-Gawad, M.S. El-Gaby, H.M. Aly, Novel antitumor acetamide, pyrrole, pyrrolopyrimidine, thiocyanate, hydrazone, pyrazole, isothiocyanate and thiophene derivatives containing a biologically active pyrazole moiety, Arzneimittel-Forschung. 59 (2009) 666-671. DOI: 10.1055/s-0031-1296457.
[10] M.H. Jung, H. Kim, W.K. Choi, M.I. El-Gamal, J.H. Park, K.H. Yoo, T.B. Sim, S.H. Lee, D. Baek, J.M. Hah, J.H. Cho, C.H. Oh, Synthesis of pyrrolo [2, 3-d] pyrimidine derivatives and their antiproliferative activity against melanoma cell line, Bioorg. Med. Chem. Lett. 19 (2009) 6538-6543. https://doi.org/10.1016/j.bmcl.2009.10.051.
[11] Y. Asukai, A. Valladares, C. Camps, E. Wood, K. Taipale, J. Arellano, A. Cassinello, J.A. Sacristán, T. Dilla, Synthesis of pyrrolo [2, 3-d] pyrimidine derivatives and their antiproliferative activity against melanoma cell line, BMC Cancer. 10 (2010) 6538-6543. https://doi.org/10.1016/j.bmcl.2009.10.051.
[12] T. McHardy, J.J. Caldwell, K.-M. Cheung, L.J. Hunter, K. Taylor, M. Rowlands, R. Ruddle, A. Henley, A. de-Haven Brandon, M. Valenti, T.G. Davies, L. Fazal, L. Seavers, F.I. Raynaud, S.A. Eccles, G.W. Aherne, M.D. Garrett, I. Collins, Discovery of 4-amino-1-(7 H-pyrrolo [2, 3-d] pyrimidin-4-yl) piperidine-4-carboxamides as selective, orally active inhibitors of protein kinase B (Akt), J. Med. Chem. 53 (2010) 2239-2249. https://doi.org/10.1021/jm901788j.
[13] M.S. Mohamed, R.A. El-Domany, R.H. Abd El-Hameed, Synthesis of certain pyrrole derivatives as antimicrobial agents, Acta Pharm. 59 (2009) 145-158. https://doi.org/10.2478/v10007-009-0016-9.
[14] Magaldi S., Mata-Essayag S., Hartung de Capriles C., Perez C., Colella M., Olaizola C. and Ontiveros Y., Well diffusion for antifungal susceptibility testing, Int J of Infectious Diseases. 1 (2004) 39-45. doi:10.1016/j.ijid.2003.03.002.
[15] Adeyemi A. I., Vincent I. I., and Olujenyo O. M., Phytochemical screening and antifungal activity of Chromolaena odorata extracts against isolate of Phytophthora megakarya using agar-well diffusion method, Asian J of Med and Bio Res. 4:1 (2018), 7-13. doi:10.3329/ajmbr.v4i1.36815.
[16] Kumar A. and Mishra A., Synthesis and antimicrobial activity of some new diphenylamine derivatives, J of Pharma and Bioallied Sci. 7:1 (2015):81.
doi:10.4103/0975-7406.148774.
[17] Nath A. R. and Reddy M. S., Design, Synthesis, Antibacterial and Antifungal Activity of Novel 2-[(E)-2-aryl-1-ethenyl]-3-(2-sulfanyl-1H-benzo[d]imidazole-5-yl)-3,4- dihydro-4-quinolinones, E-J. of Chem. 9:3 (2012) 1481-1489. doi:10.1155/2012/795698.
[18] Marimuthu alias Antonysamy J., Janarthanan G., Arumugam S., Narayanan J. and Mani N., Antioxidant, Larvicidal, and Cytotoxic Studies on Asplenium aethiopicum (Burm. f.) Becherer, Int Scholarly Res Notices. 2014(2014). doi:10.1155/2014/876170.
[19] Abbott W. S., A Method of Computing the Effectiveness of an Insecticide, J. of Eco Entomology. 18:2 (1925) 265. doi:10.1093/jee/18.2.265a.
[20] A. R. Moosavi-Zare, H. Goudarziafshar, K. Saki, Synthesis of pyranopyrazoles using nano-Fe-[phenylsalicylaldiminemethylpyranopyrazole]Cl2 as a new Schiff base complex and catalyst, Applied Organometallic Chemistry. 32.1 (2017) e3968. https://doi.org/10.1002/aoc.3968.
[21] M. Singh, A. K. Paul, V. Singh, Isatin as a 2-aminobenzaldehyde surrogate: transition metal-free efficient synthesis of 2-(2′-aminophenyl) benzothiazole derivatives, Org & Biomolecular Chem. 18:23 (2020) 4459-4469. doi:10.1039/d0ob00888e.
[22] S. M. Abd El-Hamid, S. A. Sadeek, W. A. Zordok, W. H. El-Shwiniy, W. H., Synthesis, spectroscopic studies, DFT calculations, cytotoxicity and antimicrobial activity of some metal complexes with ofloxacin and 2,2′-bipyridine, J. of Mol Str. (2018). doi:10.1016/j.molstruc.2018.08.08.
[23] Singh M., Paul A. K. and Singh V., Isatin as a 2-aminobenzaldehyde surrogate: transition metal-free efficient synthesis of 2-(2′-aminophenyl) benzothiazole derivatives, Org & Biomol. Chem., 18:23 (2020) 4459. doi:10.1039/d0ob00888e.
[24] Abd El-Hamid S. M., Sadeek S. A., Zordok W. A. and El-Shwiniy W. H., Synthesis, spectroscopic studies, DFT calculations, cytotoxicity and antimicrobial activity of some metal complexes with ofloxacin and 2,2′-bipyridine, J. of Mole Str. 1176 (2019) 422-433. doi:10.1016/j.molstruc.2018.08.08.
[25] El Sayed Aly M. R., Abd El Razek Fodah H. H. and Saleh S. Y., Antiobesity, antioxidant and cytotoxicity activities of newly synthesized chalcone derivatives and their metal complexes, Eur. J. of Med. Chem. 76 (2014): 517-530. doi:10.1016/j.ejmech.2014.02.021.
[26] Milbeo P., Quintin F., Moulat L., Didierjean C., Martinez J., Bantreil X. and Lamaty F., Synthesis, characterisation and cytotoxic activity evaluation of new metal-salen complexes based on the 1,2-bicyclo[2.2.2]octane bridge, Tetrahedron Letters. 63 (2021): 152706. doi:10.1016/j.tetlet.2020.152706.
[27] Guney E., Yilmaz V. T., Ari F., Buyukgungor O. and Ulukaya E.,Synthesis, characterization, structures and cytotoxic activity of palladium(II) and platinum(II) complexes containing bis(2-pyridylmethyl)amine and saccharinate, Polyhedron. 30, no. 1 (2011) 114-122. doi:10.1016/j.poly.2010.09.037.
[28] Atta E. M., Hegab K. H., Abdelgawad A. A. M. and Youssef A. A., Synthesis, characterization and cytotoxic activity of naturally isolated naringin-metal complexes, Saudi Pharmaceutical J. 27:4 (2019): 584-592. doi:10.1016/j.jsps.2019.02.006