Medicinal Chemistry Research

, Volume 28, Issue 10, pp 1601–1617 | Cite as

Synthesis, antimicrobial evaluation, and molecular docking of some new angular allylbenzochromone derivatives

  • El-Sayed I. El-DesokyEmail author
  • Aya A. El-Sawi
  • Mohamed A. Abozeid
  • Mohamed Abdelmoteleb
  • Mona Shaaban
  • Eman M. Keshk
  • Abdel-Rahman H. Abdel-Rahman
Original Research


Different classes of antimicrobial compounds such as β-lactams, sulfonamides, aminoglycosides, tetracyclines, quinolines and others have been developed during the 20th century to control the growing antimicrobial resistance. Therefore, there is an urgent need to build up new and effective antimicrobial agents with different working mechanisms to suppress this resistance. Accordingly, the judicious design of antimicrobial organic compounds with antiquorum-sensing activities could be a major solution for this global challenge. Herein, the versatile precursor 6-allyl-3-formyl-4H-benzo[h]chromen-4-one (2) was used for the synthesis of various isolated and condensed naphthoyl or (chromenyl) nicotinonitriles, azalactone, thiazolidinone, xanthene, indenopyridine, Schiff bases, diazepine, imidazole and triazolopyrimidine derivatives 5-21via its reactions with several active carbon nucleophiles in addition to amines, benzil and hydrazine. Some of the newly synthesized compounds showed moderately and good antimicrobial activities. The compounds 2 and 14 were the best concerning effects. In addition, the antiquorum-sensing activities of the newly prepared compounds were assessed against Chromobacterium violaceum. Specifically, pharmaceutical evaluation, antimicrobial prediction, and molecular docking using computational tools illustrated that the complexes of the latter compounds may show substantial antimicrobial activity in comparison with the other derivatives.

New angular allylbenzochromones were synthesized, and their antimicrobial plus antiquorum-sensing activities were evaluated to give 3-formylchrmone 2 and tetracarbonyl 14 as the best antimicrobials. Computational prediction of pharmacokinetics, drug-likeness properties, biological activity, and molecular docking suggested that formyl chromone 2 and tetracarbonyl 14 may be potent antimicrobial drugs.


Chromone Naphthyl Antimicrobial activity Antiquorum-sensing Docking 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Abdel-Rahman SA, El-Gohary NS, El-Bendary ER, El-Ashry SM, Shaaban MI (2017) Synthesis, antimicrobial, antiquorum-sensing, antitumor and cytotoxic activities of new series of cyclopenta(hepta)[b]thiophene and fused cyclohepta[b]thiophene analogs. Eur J Med Chem 140:200–211Google Scholar
  2. Andrews JM (2001) Determination of minimum inhibitory concentrations. J Antimicrob Chemother 48:5–16CrossRefGoogle Scholar
  3. Bhardwaj AK, Vinothkumar K, Rajpara N (2013) Bacterial quorum sensing inhibitors: attractive alternatives for control of infectious pathogens showing multiple drug resistance. Recent Pat Antiinfect Drug Discov 8:68–83CrossRefGoogle Scholar
  4. Daina A, Zoete V (2016) A BOILED‐egg to predict gastrointestinal absorption and brain penetration of small molecules. Chem Med Chem 11:1117–1121CrossRefGoogle Scholar
  5. Daina A, Michielin O, Zoete V (2014) iLOGP: a simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach. J Chem Inf Model 54:3284–3301CrossRefGoogle Scholar
  6. Daina A, Michielin O, Zoete V (2017) SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 7:42717Google Scholar
  7. Dua R, Shrivastava S, Sonwane SK, Srivastava SK (2011) Pharmacological significance of synthetic heterocycles scaffold: a review. Adv Biol Res 5:120–144Google Scholar
  8. El-Desoky SI, Keshk EM, El-Sawi AA, Abozeid MA, Abouzeid LA, Abdel-Rahman ARH (2018) Synthesis, biological evaluation and in silico molecular docking of novel 1-hydroxy-naphthyl substituted heterocycles. Saudi Pharm J 26:852–859Google Scholar
  9. Ellis GP (1977) Chromenes, chromanones and chromones. John Willy & Sons, New YorkGoogle Scholar
  10. Ghosh CK, Khan S (1981) Heterocyclic systems; 101. Defunct 4-oxo-4H-[1] benzopyran-3-carboxylic acids -3-carboxaldehydes. Synthesis 1981:719–721Google Scholar
  11. Holt RJ (1975) Laboratory tests of antifungal drugs. J Clini Pathol 28:767–774CrossRefGoogle Scholar
  12. Karad SC, Purohit VB, Thummar RP, Vaghasiya BK, Kamani RD, Thakor P, Raval DK (2017) Synthesis and biological screening of novel 2-morpholinoquinoline nucleus clubbed with 1,2,4-oxadiazole motifs. Eur J Med Chem 126:894–909CrossRefGoogle Scholar
  13. Martin YC (2005) A bioavailability score. J Med Chem 48:3164–3170CrossRefGoogle Scholar
  14. McClean R, Pierson LS, Fuqua C (2004) A simple screening protocol for the identification of quorum signal antagonists. J Microbiol Methods 58:351–360CrossRefGoogle Scholar
  15. McClean KH, Winson MK, Fish L, Taylor A, Chhabra SR, Camara M, Stewart GS (1997) Quorum sensing and chromobacterium violaceum: exploitation of violacein production and inhibition for the detection of N-acylhomoserine lactones. Microbiology 143:3703–3711CrossRefGoogle Scholar
  16. Mohamed GA, Ibrahim SR, Shaaban MI, Ross SA (2014) Mangostanaxanthones I and II, new xanthones from the pericarp of Garcinia mangostana. Fitoterapia 98:215–221CrossRefGoogle Scholar
  17. Osman KT, Du L, He Y, Luo Y (2009) Crystal structure of Bacillus cereus D-alanyl carrier protein ligase (DltA) in complex with ATP. J Mol Biol 388:345–355CrossRefGoogle Scholar
  18. Parasuraman S (2011) Prediction of activity spectra for substances. J Pharm Pharm 2:52–53Google Scholar
  19. Parsons ZD, Bland JM, Mullins EA, Eichman BF (2016) A catalytic role for C–H/π interactions in base excision repair by Bacillus cereus DNA glycosylase AlkD. J Am Chem Soc 138:11485–11488CrossRefGoogle Scholar
  20. Pearson RD, Steigbigel RT, Davis HT, Chapman SW (1980) Method of reliable determination of minimal lethal antibiotic concentrations. Antimicrob Agents Chemother 18:699–708CrossRefGoogle Scholar
  21. Rex JH, Alexander BD, Andes D, Arthington-Skaggs B, Brown SD, Chaturvedi V, Ghannoum MA, Espinel-Ingroff A, Knapp CC, Ostrosky-Zeichner L, Pfaller MA, Sheehan DJ, Walsh TJ (2008) Reference method for Broth dilution antifungal susceptibility testing of yeasts; approved standard-third edition. Clinical and Laboratory Standards Institute. CLSI document M27-A3Google Scholar
  22. Rex JH, Alexander BD, Andes D, Arthington-Skaggs B, Brown SD, Chaturveli V, Espinel-Ingroff A, Ghannoum MA, Knapp CC, Motyl MR, Ostrosky-Zeichner L, Pfaller M, Sheehan DJ, Walsh TJ (2008) Reference method for Broth dilution antifungal susceptibility testing of filamentous fungi; approved standard-second edition. Clinical and Laboratory Standards Institute. CLSI document M38-A2Google Scholar
  23. Risitano F, Grassi G, Foti F (2001) Reactions of 3‐substituted chromones with ortho‐phenylenediamine. J Heterocycl Chem 38:1083–1086CrossRefGoogle Scholar
  24. Rodríguez M, Santillan R, López Y, Farfán N, Barba V, Nakatani K, García Baéz EV, Padilla-Martinez II (2007) N–H…O Assisted structural change sinduced on ketoenamine systems. Supramol Chem 19:641–653CrossRefGoogle Scholar
  25. Sapariya NH, Vaghasiya BK, Thummar RP, Kamani RD, Patel KH, Thakor P, Thakkar SS, Ray A, Raval DK (2017) Synthesis, characterization, in silico molecular docking study and biological evaluation of a 5-(phenylthio) pyrazole based polyhydroquinoline core moiety. New J Chem 41:10686–10694CrossRefGoogle Scholar
  26. Savjani KT, Gajjar AK, Savjani JK (2012). Drug solubility: importance and enhancement techniques. ISRN pharm. 2012: Article ID 195727Google Scholar
  27. Sigg I, Haas G, Winkler T (1982) The reaction of 3‐formylchromone with ortho‐substituted anilines. Preparation of a tetraaza[14]annulene. Helv Chim Acta 65:275–279CrossRefGoogle Scholar
  28. Thakkar SS, Thakor P, Ray A, Doshi H, Thakkar VR (2017) Benzothiazole analogues: synthesis, characterization, MO calculations with PM6 and DFT, in silico studies and in vitro antimalarial as DHFR inhibitors and antimicrobial activities. Bioorg Med Chem 25:5396–5406Google Scholar
  29. Trott O, Olson AJ (2010) AutoDock vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455–461Google Scholar
  30. Vandeputte OM, Kiendrebeogo M, Rajaonson S, Diallo B, Mol A, El Jaziri M, Baucher M (2010) Identification of catechin as one of the flavonoids from Combretum albiflorum bark extract that reduces the production of quorum-sensing-controlled virulence factors in Pseudomonas aeruginosa PAO1. Appl Environ Microbiol 76:243–253CrossRefGoogle Scholar
  31. Patel JB, Cockerill FR, Bradford PA, Eliopoulos GM, Hindler JA, Jenkins SG, Lewis JS, Limbago B, Miller LA, Nicolau DP, Powell M, Swenson JM, Traczewski MM, Turnidge JD, Weinstein MP, Zimmer BL (2015) Performance standards for antimicrobial susceptibility testing; 25th informational supplement. CLSI document M100-S25. Clinical and Laboratory Standards Institute, WayneGoogle Scholar
  32. Yahiaoui S, Fagnere C, Pouget C, Buxeraud J, Chulia AJ (2008) New 7, 8-benzoflavanones as potent aromatase inhibitors: synthesis and biological evaluation. Bioorg Med Chem 16:1474–1480CrossRefGoogle Scholar
  33. Yang H, Lou C, Sun L, Li J, Cai Y, Wang Z, Tang Y (2018) admetSAR 2.0: web-service for prediction and optimization of chemical ADMET properties. Bioinformatics 35:1067–1069CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Chemistry, Faculty of ScienceMansoura UniversityMansouraEgypt
  2. 2.Food Allergy Research & Resource Program (FARRP), Department of Food Science & TechnologyUniversity of NebraskaLincolnUSA
  3. 3.Department of Botany, Faculty of ScienceMansoura UniversityMansouraEgypt
  4. 4.Department of Microbiology, Faculty of PharmacyMansoura UniversityMansouraEgypt

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