Mannich bases derivatives of 2-Phenyl-5-Benzimidazole sulfonic acid; Synthesis, Characterization, Computational studies and Biological evaluation
DOI:
https://doi.org/10.1590/s2175-97902023e19544Keywords:
Benzimidazole; Mannich bases; Antioxidant activity; Cytotoxicity activity; α-glucosidase activity; α-Amylase activity; Molecular DockingAbstract
A new series of N-Mannich bases of 2-Phenyl-5-benzimidazole sulfonic acid have been synthesized through amino methylation reaction with secondary amines. The two moieties were held together through a methylene bridge, which comes from formaldehyde (Formalin Solution 37%) used in the reaction. Chemical structures of the newly synthesized compounds have been confirmed using FT-IR, 1HNMR and 13CNMR. Different in vitro assays including Anti-oxidant, Enzyme inhibition, Anti-microbial and Cytotoxicity assay were performed to evaluate the biological potential with reference to the standard drug. Among the synthesized library, compound 3a shows maximum alpha-glucosidase inhibition with an IC50 value of 66.66 μg/ml, compound 3d was found most toxic with LC50 value of 10.17 μg/ml. ADME evaluation studies were performed with the help of Molinspiration online software. Docking calculations were also performed. Given the importance of the nucleus involved, the synthesized compound might find extensive medicinal applications as reported in the literature.
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Ahmed M, Fatima H, Qasim M, Gul B. Polarity directed optimization of phytochemical and in vitro biological potential of an indigenous folklore: Quercus dilatata Lindl. ex Royle. BMC Complement Altern Med. 2017 Dec 1;17(1):386.
Adegboye AA, Khan KM, Salar U, Aboaba SA, Chigurupati S, Fatima I, et al. 2-Aryl benzimidazoles: Synthesis, In vitro α-amylase inhibitory activity, and molecular docking study. Eur J Med Chem. 2018 Apr 25;150:248-60.
Ayyappan S, Philip S, Bharathy N, Ramesh V, Kumar CN, Swathi S, et al. Antioxidant status in neonatal jaundice before and after phototherapy. J Pharm Bioallied Sci. 2015 Apr;7(Suppl 1):S16.
Bibi Y, Nisa S, Chaudhary FM, Zia M. Antibacterial activity of some selected medicinal plants of Pakistan. BMC Complement Altern Med . 2011 Dec 1;11(1):52.
Bérdy J. Thoughts and facts about antibiotics: where we are now and where we are heading. The J Antibiot. 2012 Aug;65(8):385-95.
Cho KS, Talapin DV, Gaschler W, Murray CB. Designing PbSe nanowires and nanorings through oriented attachment of nanoparticles. J Am Chem Soc. 2005 May 18;127(19):7140-7.
Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. In Chemical biology 2015 (pp. 243-250). Humana Press, New York, NY.
Faizi M, Jahani R, Ebadi SA, Tabatabai SA, Rezaee E, Lotfaliei M, et al. Novel 4-thiazolidinone derivatives as agonists of benzodiazepine receptors: design, synthesis and pharmacological evaluation. EXCLI J. 2017;16:52.
Fatima H, Khan K, Zia M, Ur-Rehman T, Mirza B, Haq IU. Extraction optimization of medicinally important metabolites from Datura innoxia Mill.: an in vitro biological and phytochemical investigation. BMC Complement Altern Med . 2015 Dec 1;15(1):376.
Husain A, Ahmad A, Khan SA, Asif M, Bhutani R, Al-Abbasi FA. Synthesis, molecular properties, toxicity and biological evaluation of some new substituted imidazolidine derivatives in search of potent anti-inflammatory agents. Saudi Pharm J. 2016 Jan 1;24(1):104-14.
Hodgkin DC, Pickworth J, Robertson JH, Trueblood KN, Prosen RJ, White JG. Structure of vitamin B12: the crystal structure of the hexacarboxylic acid derived from B12 and the molecular structure of the vitamin. Nature. 1955 Aug 20;176(4477):325-8.
Hamama WS, Zoorob HH, Gouda MA, Afsah EM. Synthesis and antimicrobial and antioxidant activities of simple saccharin derivatives with N-basic side chains. Pharm Chem J. 2011 May 1;45(2):118-24.
Huttunen KM, Rautio J. Prodrugs-an efficient way to breach delivery and targeting barriers. Curr Top Med Chem. 2011 Sep 1;11(18):2265-87.
Joshi S, Manikpuri AD, Tiwari P. Synthesis and biological study of medicinally important Mannich bases derived from 4-(dimethylamino)-1, 4, 4a, 5, 5a, 6, 11, 12a-octahydro-3, 6, 10, 12, 12a pentahydroxy naphthacene carboxamide. Bioorg Med Chem Lett. 2007 Feb 1;17(3):645-8.
Kim JS, Kwon CS, Son KH. Inhibition of alpha-glucosidase and amylase by luteolin, a flavonoid. Biosci Biotechnol Biochem. 2000;64(11):2458-61.
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 1997 Jan 15;23(1-3):3-25.
Nair SS, Kavrekar V, Mishra A. In vitro studies on alpha amylase and alpha glucosidase inhibitory activities of selected plant extracts. Eur J Exp Biol. 2013;3(1):128-32.
Notz W, Tanaka F, Watanabe SI, Chowdari NS, Turner JM, Thayumanavan R, Barbas CF. The direct organocatalytic asymmetric Mannich reaction: unmodified aldehydes as nucleophiles. J Org Chem. 2003 Dec 12;68(25):9624-34.
Saab AN, Sloan KB, Beall HD, Villanueva R. Effect of Aminomethyl (N-Mannich Base) Derivatization on the Ability of S6Acetyloxymethyl-S-Mercaptopurine Prodrug to Deliver 6-Mercaptopurine through Hairless Mouse Skin. J Pharm Sci. 1990 Dec 1;79(12):1099-104.
Shahwar D, Raza MA, Saeed A, Riasat M, Chattha FI, Javaid M, et al. Antioxidant potential of the extracts of Putranjiva roxburghii, Conyza bonariensis, Woodfordia fruiticosa and Senecio chrysanthemoids. Afr J Biotechnol. 2012;11(18):4288-95.
Waters B, Saxena G, Wanggui Y, Kau D, Wrigley S, Stokes R, Davies J. Identifying protein kinase inhibitors using an assay based on inhibition of aerial hyphae formation in Streptomyces. J Aantibiot. 2002 Apr 25;55(4):407-16.
Zahra SS, Ahmed M, Qasim M, Gul B, Zia M, Mirza B, et al. Polarity based characterization of biologically active extracts of Ajuga bracteosa Wall. ex Benth. and RP-HPLC analysis. BMC Complement Altern Med . 2017 Dec;17(1):1-6.
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