DESIGN, SYNTHESIS, MOLECULAR DOCKING, AND EVALUATION OF CHROMONE BASED TETRAZOLE DERIVATIVES
DOI:
https://doi.org/10.22159/ajpcr.2019.v12i3.30860Keywords:
Chromone, VilsmeierHaack, Antibacterial, Antifungal, 2-Anilino-3-formylchromones, Tetrazole, DNA gyraseAbstract
Objectives: The objective of this research work was to design, synthesize, study the molecular docking, and evaluate the antimicrobial activity of some novel substituted 2-(Phenylamino)-3-(1H-tetrazol-5-yl)-4H-chromen-4-one derivatives (12a-h).
Methods: In the present work, 3-Formylchromones were transformed into pharmacologically active substituted 2-(Phenylamino)-3-(1H-tetrazol-5- yl)-4H-chromen-4-one derivatives (12a-h) through a multistep reaction. Initially, synthesis of the substituted 4-Oxo-2-(phenylamino)-4H-chromone-3- carbaldehydes (9a-h) was carried out using substituted acetophenones (6a-h) as starting material and by employing an earlier reported method (1,3-dipolar cycloaddition reaction). Then, these synthesized compounds were converted into respective oximes (10a-h).The obtained oximes (10a-h) were further converted into nitriles (11a-h) which were finally subjected to concerted cycloaddition through stepwise addition of neutral or anionic azide species to furnish final substituted 2-(Phenylamino)-3-(1H-tetrazol-5-yl)-4H-chromen-4-one derivatives (12a-h). All the newly synthesized compounds (12a-h) and a reference compound (ciprofloxacin) were docked into the active site of TyrRS (PDB: 1JIK) by means of the BioPredicta module of VLife MDS. The synthesized compounds (12a-h) were also evaluated in vitro for their antibacterial (against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli bacterial stains) and antifungal activities (against Aspergillus niger and Candida albicans fungal strains) using Zone of Inhibition method.
Results: The formation of substituted 2-(Phenylamino)-3-(1H-tetrazol-5-yl)-4H-chromen-4-one derivatives (12a-h) was confirmed through their spectral analysis, that is, 1H-NMR, 13C-NMR, and Mass spectroscopy. During docking study, the recorded molecular binding interactions revealed that all the newly synthesized compounds (12a-h) interacted well with binding site of the enzyme. The synthesized compounds were also evaluated in vitro for their antibacterial (against S. aureus, B. subtilis, P. aeruginosa, and E. coli bacterial stains) and antifungal activities (against A. niger and C. albicans fungal strains). All the synthesized compounds exhibited moderate-to-potent antimicrobial activities.
Conclusions: All the synthesized compounds exhibited moderate-to-potent antimicrobial activity.
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Singh B, Sharma V, Singh G, Kumar R, Arora S, Ishar MP, et al. Synthesis and in vitro cytotoxic activity of chromenopyridones. Int J Med Chem 2013;2013:984329.
Valdameri G, Genoux-Bastide E, Peres B, Gauthier C, Guitton J, Terreux R, et al. Substituted chromones as highly potent nontoxic inhibitors, specific for the breast cancer resistance protein. J Med Chem 2012;55:966-70.
Gaspar A, Silva T, Yáñez M, Vina D, Orallo F, Ortuso F, et al. Chromone, a privileged scaffold for the development of monoamine oxidase inhibitors. J Med Chem 2011;54:5165-73.
Ramos FA, Takaishi Y, Shirotori M, Kawaguchi Y, Tsuchiya K, Shibata H, et al. Antibacterial and antioxidant activities of quercetin oxidation products from yellow onion (Allium cepa) skin. J Agric Food Chem 2006;54:3551-7.
Goel R, Sharma V, Budhiraja A, Ishar MP. Synthesis and evaluation of novel 3a,9a-dihydro-1-ethoxycarbonyl-1-cyclopenteno[5,4-b]benzopyran-4-ones as antifungal agents. Bioorg Med Chem Lett 2012;22:4665-7.
Kuroda M, Uchida S, Watanabe K, Mimaki Y. Chromones from the tubers of Eranthis cilicica and their antioxidant activity. Phytochemistry 2009;70:288-93.
Brinkworth RI, Stoermer MJ, Fairlie DP. Flavones are inhibitors of HIV-1 proteinase. Biochem Biophys Res Commun 1992;188:631-7.
Sandhya B, Vinod M, Lohitha P, Ashwini T, Shravani A. Synthesis, characterization and pharmacological activities of coumarin derivatives. Int J Chem Pharm Sci 2010;1:16-25.
Kumar PB, Yerrabelly H, Yerrabelly JR. Synthesis and anti-microbial/anti-malarial activity of a new class of chromone-dihydroquinazolinone hybrid heterocycles. ARKIVOC 2018;3:212-8.
Galal SA, El-All AS, Abdallah MM, El-Diwani HI. Synthesis of potent antitumor and antiviral benzofuran derivatives. Bioorg Med Chem Lett 2009;19:2420-4.
Hanna AT, Ewies EF, Wageeh SE. Synthesis of chromones and their applications during the last ten years. Int J Res Pharm Chem 2014;4:1046-85.
Serge K, Hubert GT, Janine B, Pierre B, Marie M. Synthesis and evaluate the anti-allergic and antihistamine activity of benzyl-3-chromones (homo-isoflavones). Eur J Med Chem 1989;24:541-6.
Hatzade K, Taile V, Gaidhane P, Ingle V. Synthesis, structural determination, and biological activity of new 7-hydroxy-3-pyrazolyl-4H-chromen- 4-ones and their o-beta-D-glucosides. Turk J Chem 2010;34:241-54.
Sashidhara KV, Kumar A, Kumar M, Sarkar J, Sinha S. Synthesis and in vitro evaluation of novel coumarin-chalcone hybrids as potential anticancer agents. Bioorg Med Chem Lett 2010;20:7205-11.
Kawase M, Tanaka T, Kan H, Tani S, Nakashima H, Sakagami H, et al. Biological activity of 3-formylchromones and related compounds. In vivo 2007;21:829-34.
Ali TE, Magdy AI, Eman ME, Zeinab ME. Proceedings in 16th International Electronic Conference on Synthetic Organic Chemistry. Egypt; 2012. p. 1-15.
Mazimba O. Antimicrobial activities of heterocycles derived from thienylchalcones. J King Saudi Univ Sci 2015;15:27-48.
Singh G, Sharma S. Synthesis and antimicrobial activity of thiosemicarbazone induced hydrazone of 2-Anilino-3-formylchromone. J Chem Pharm Res 2015;7:599-605.
Singh G, Singh R, Girdhar NK, Ishar MP. A versatile route to 2-alkyl-/aryl-amino-3-formyl- and hetero-annelated-chromones, through a facile nucleophilic substitution at C2 in 2-(N-methylanilino)-3-formylchromones. Tetrahedron 2002;58:2471-80.
Singh G, Singh G, Ishar MP. Pericyclic Transformations at the periphery of chromen-4-one (=4H-1-benzopyran-4-one): An unusual preference for a 1,5-shift of allylic moieties over the ene reaction. Synlett 2003;86:256-8.
Singh G, Singh L, Ishar MP. 2-(N-Methylanilino)-3-formylchromone- a versatile synthon for incorporation of chromone moiety in a variety of heterocyclic systems and macrocycles through reactions with bifunctional nucleophiles. Tetrahedron 2002;58:7883-90.
Ishar MP, Singh G, Singh S, Sreenivasan KK, Singh G. Design, synthesis, and evaluation of novel 6-chloro-/fluorochromone derivatives as potential topoisomerase inhibitor anticancer agents. Bioorg Med Chem Lett 2006;16:1366-70.
Ibrahim SS, Allimony HA, Abdel-Halim AM, Ibrahim AM. Synthesis and reactions of 8-allylchromone-3-carboxaldehyde. ARKIVOC 2009;14:28-38.
Ahmed B, Samad A, Hasan M. Molecular modelling studies, synthesis and antimicrobial screening of some novel sulphonamide quinazolin-4(3h)-one fused derivatives. Int J Pharm Pharm Sci 2014;6:312-7.
Ramya TS, Sathyanathan T, Kumar PD, Chowdhari M. Docking studies on synthesized quinazoline compounds on androgen receptor. Int J Pharm Ind Res 2011;1:266-9.
Kumar HK, Parmeshwar H. Synthesis, molecular docking and antibacterial evaluation of some novel N-4 piperidinyl derivatives of sparfloxacin. Asian J Pharm Clin Res 2018;11:415-21.
Ramanjaneyulu K, Bindhu JH, Naaz TU, Prasad VV, Satya BL. Synthesis, antioxidant, antibacterial and cytotoxic activity of novel chromone derivatives. Pharm Chem 2017;9:78-89.
Walmik P, Naraboli BS, Swathi B, Ghanti S. Design, synthesis of biologically active heterocycles containing indol-thiazolyl-thiazolidinone derivatives. Asian J Pharm Clin Res 2017;11:113-7.
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