Saima KALSOOM, Abdul HAMEED, Abbas HASSAN, Shaista PARVEEN, Rifhat BIBI, Ambreen ASGHAR, Waqar AHMED

Computational and biological studies of novel thiazolyl coumarin derivatives synthesized through Suzuki coupling

The current investigation presents the synthesis, computational molecular-docking and biological activity studies of arylated thiazole coumarins. Aryl substituted thiazolyl coumarin derivatives were synthesized via Suzuki cross-coupling reaction. A detailed reaction condition optimization revealed that the Pd-PEPPSI-IPent precatalyst in only 2 mol% loading resulted in the desired product with high yield. The aim of this study was to examine the antimicrobial behavior of thiazole coumarin derivatives through in vitro and in silico studies. All the compounds showed activity against both antibacterial strains, Staphylococcus aureus and Escherichia coli, except 5d. Similarly, the compounds 5a, 5b, and 5d were found to be active against Trichoderma harzianum. The compound 5d of this series was found to have a higher activity with MIC 125 mg/ml against Trichoderma harzianum. Molecular studies showed the high activities of these compounds are due to the presence of strong H-bonding and π-π interaction with their respective targets. A good correlation was observed between computational and in vitro studies.

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1. Brockhurst MA, Harrison F, Veening J-W, Harrison E, Blackwell G et al. Assessing evolutionary risks of resistance for new antimicrobial therapies. Nature Ecology & Evolution 2019; 3 (4): 515-517. doi: 10.1038/s41559-019-0854-x
2. Cattoir V, Felden B. Future antibacterial strategies: from basic concepts to clinical challenges. The Journal of Infectious Diseases 2019; 220(3): 350-360. doi: 10.1093/infdis/jiz134
3. Fair RJ, Tor Y. Antibiotics and bacterial resistance in the 21st century. Perspectives in Medicinal Chemistry 2014; 6: PMC.S14459. doi:10.4137/pmc.s14459
4. Tang H, Zheng C, Lv J, Wu J, Li Y et al. Synthesis and antifungal activities in vitro of novel pyrazino [2,1-a] isoquinolin derivatives.Bioorganic & Medicinal Chemistry Letters 2010; 20 (3): 979-982. doi: 10.1016/j.bmcl.2009.12.050
5. Wang W, Sheng C, Che X, Ji H, Miao Z et al. Design, synthesis, and antifungal activity of novel conformationally restricted triazole derivatives. Archiv der Pharmazie 2009; 342 (12): 732-739. doi: 10.1002/ardp.200900103
6. Mahesh TC, Shivani P, Palmi M, Pathik SB. Thiazole: a Review on chemistry, synthesis and therapeutic importance of its derivatives. Current Topics in Medicinal Chemistry 2016; 16 (26): 2841-2862. doi: 10.2174/1568026616666160506130731
7. Ayati A, Emami S, Asadipour A, Shafiee A, Foroumadi A. Recent applications of 1,3-thiazole core structure in the identification of new lead compounds and drug discovery. European Journal of Medicinal Chemistry 2015; 97: 699-718. doi: 10.1016/j.ejmech.2015.04.015
8. Ioannis F, Dimitra Hadjipavlou L. Hybrids of coumarin derivatives as potent and multifunctional bioactive agents: areview. Medicinal Chemistry 2019; 15: 1-36. doi: 10.2174/1573406415666190416121448
9. Borges F, Roleira F, Milhazes N, Santana L, Uriarte E. Simple coumarins and analogues in medicinal chemistry: occurrence, synthesis and biological activity. Current Medicinal Chemistry 2005; 12 (8): 887-916. doi: 10.2174/0929867053507315
10. Grover J, Jachak SM. Coumarins as privileged scaffold for anti-inflammatory drug development. RSC Advances 2015; 5 (49): 38892-38905.doi: 10.1039/C5RA05643H
11. Ibrar A, Tehseen Y, Khan I, Hameed A, Saeed A et al. Coumarin-thiazole and -oxadiazole derivatives: synthesis, bioactivity and docking studies for aldose/aldehyde reductase inhibitors. Bioorganic Chemistry 2016; 68: 177-186. doi: 10.1016/j.bioorg.2016.08.005
12. Prashanth T, Avin BRV, Thirusangu P, Ranganatha VL, Prabhakar BT et al. Synthesis of coumarin analogs appended with quinoline and thiazole moiety and their apoptogenic role against murine ascitic carcinoma. Biomedicine and Pharmacotherapy 2019; 112: 108707. doi: 10.1016/j.biopha.2019.108707
13. Mohareb RM, Ho JZ, Mohamed AA. Uses of 1-Cyanoacetyl-4-phenyl-3-thiosemicarbazide in Heterocyclic Synthesis: synthesis of thiazole, coumarin, and pyridine derivatives with antimicrobial and antifungal activities. Phosphorus, Sulfur, and Silicon and the Related Elements 2007; 182 (8): 1661-1681. doi: 10.1080/10426500701289914
14. Kumar S, Saini V, Maurya IK, Sindhu J, Kumari M et al. Design, synthesis, DFT, docking studies and ADME prediction of some new coumarinyl linked pyrazolylthiazoles: potential standalone or adjuvant antimicrobial agents. PLoS One 2018; 13 (4): e0196016. doi: 10.1371/journal.pone.0196016
15. Prieto-Martínez FD, López-López E, Eurídice Juárez-Mercado K and Medina-Franco JL. Computational drug design methods—current and future perspectives. In: Roy K (editor). In Silico Drug Design. London, UK: Academic Press, 2019, pp. 19-44.
16. Leelananda SP, Lindert S. Computational methods in drug discovery. Beilstein Journal of Organic Chemistry 2016; 12: 2694-2718. doi:10.3762/bjoc.12.267
17. Pinzi L, Rastelli G. Molecular docking: shifting paradigms in drug discovery. International Journal of Molecular Sciences 2019; 20 (18):4331.
18. Parveen S, Shah MS, Zaib S, Gul T, Khan KM et al. Modification of Bischler-Möhlau indole derivatives through palladium catalyzed Suzuki reaction as effective cholinesterase inhibitors, their kinetic and molecular docking studies. Bioorganic Chemistry 2018; 76: 166-176. doi: 10.1016/j.bioorg.2017.11.003
19. Hayat K, Afzal S, Saeed A, Murtaza A, Ur Rahman S et al. Investigation of new quinoline derivatives as promising inhibitors of NTPDases: Synthesis, SAR analysis and molecular docking studies. Bioorganic Chemistry 2019; 87: 218-226. doi: 10.1016/j.bioorg.2019.03.019
20. Ahmad H, Ullah S, Rahman F, Saeed A, Pelletier J et al. Synthesis of biphenyl oxazole derivatives via Suzuki coupling and biological evaluations as nucleotide pyrophosphatase/phosphodiesterase-1 and -3 inhibitors. European Journal of Medicinal Chemistry 2020; 208: 112759. doi: 10.1016/j.ejmech.2020.112759
21. Dinparast L, Hemmati S, Zengin G, Alizadeh AA, Bahadori MB et al. Rapid, efficient, and green synthesis of coumarin derivatives via Knoevenagel condensation and investigating their biological effects. ChemistrySelect 2019; 4 (31): 9211-9215. doi: 10.1002/slct.201901921
22. Teizo S, Koichi T. Solvent-free coumarin synthesis. Chemistry Letters 2001; 30 (2): 110-111. doi: 10.1246/cl.2001.110
23. Wang Z. Hantzsch Thiazole Synthesis. In: Comprehensive Organic Name Reactions and Reagents. New York, NY, USA: John Wiley & Sons Inc., 2010, pp. 1330-1334.
24. Hooshmand SE, Heidari B, Sedghi R, Varma RS. Recent advances in the Suzuki–Miyaura crosscoupling reaction using efficient catalysts in eco-friendly media. Green Chemistry 2019; 21 (3): 381-405. doi: 10.1039/C8GC02860E
25. Valente C, Çalimsiz S, Hoi KH, Mallik D, Sayah M et al. The development of bulky palladium NHC complexes for the most-challenging cross-coupling reactions. Angewandte Chemie International Edition 2012; 51 (14): 3314-3332. doi: 10.1002/anie.201106131
26. Price GA, Hassan A, Chandrasoma N, Bogdan AR, Djuric SW et al. Pd-PEPPSI-IPent-SiO2: a supported catalyst for challenging Negishi coupling reactions in flow. Angewandte Chemie International Edition 2017; 56 (43): 13347-13350. doi: 10.1002/anie.201708598
27. Rao VR, Rao TVP. Studies on coumarin derivatives. Part I. Synthesis of some substituted thiazolyl and benzoxazinylcoumarins. Chemischer Informationsdienst 1986; 25B (4): 413-415.
28. Boyanova L, Gergova G, Nikolov R, Derejian S, Lazarova E et al. Activity of Bulgarian propolis against 94 Helicobacter pylori strains in vitro by agar-well diffusion, agar dilution and disc diffusion methods. Journal of Medical Microbiology 2005; 54 (5): 481-483. doi: 10.1099/jmm.0.45880-0
29. Okeke MI, Iroegbu CU, Eze EN, Okoli AS, Esimone CO. Evaluation of extracts of the root of Landolphia owerrience for antibacterial activity. Journal of Ethnopharmacology 2001; 78 (2): 119-127. doi: 10.1016/S0378-8741(01)00307-5
30. Molecular Operating Environment (MOE). Montreal, QC, Canada: Chemical Computing Group Inc., 2016.
31. Surry DS, Buchwald SL. Dialkylbiaryl phosphines in Pd-catalyzed amination: a user’s guide. Chemical Science 2011; 2 (1): 27-50. doi:10.1039/C0SC00331J
32. Atwater B, Chandrasoma N, Mitchell D, Rodriguez MJ, Organ MG. Pd-PEPPSI-IHeptCl: A general-purpose, highly reactive catalyst for the selective coupling of secondary alkyl organozincs. Chemistry – A European Journal 2016; 22 (41): 14531-14534. doi: 10.1002/chem.201603603