{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:16:42Z","timestamp":1790957802009,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2022R24"],"award-info":[{"award-number":["PNURSP2022R24"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>The viral RNA-dependent RNA polymerase (RdRp) complex is used by SARS-CoV-2 for genome replication and transcription, making RdRp an interesting target for developing the antiviral treatment. Hence the current work is concerned with the green synthesis, characterization and docking study with the RdRp enzyme of the series of novel and diverse hydrazones and pyrazoles. 4-Methyl-2-(2-(1-phenylethylidene)hydrazineyl)thiazole-5-carbohydrazide was prepared and then condensed with different carbonyl compounds (aldehydes and ketones either carbocyclic aromatic or heterocyclic) afforded the corresponding hydrazide-hydrazones. The combination of the acid hydrazide with bifunctional reagents such as acetylacetone, \u03b2-ketoesters (ethyl acetoacetate and ethyl benzoylacetate) resulted in the formation of pyrazole derivatives. The synthesized compounds were all obtained through grinding method using drops of AcOH. Various analytical and spectral analyses were used to determine the structures of the prepared compounds. Molecular Operating Environment (MOE\u00ae) version 2014.09 was used to estimate interactions between the prepared thiazole\/hydrazone hybrids and RdRp obtained from the protein data bank (PDB: 7bv2) using enzyme-ligand docking for all synthesized derivatives and Remdesivir as a reference. Docking results with the RdRp enzyme revealed that the majority of the investigated drugs bind well to the enzyme via various types of interactions in comparison with the reference drug.<\/jats:p>","DOI":"10.3390\/polym14153160","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T23:33:01Z","timestamp":1659569581000},"page":"3160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Evaluation of the Binding Relationship of the RdRp Enzyme to Novel Thiazole\/Acid Hydrazone Hybrids Obtainable through Green Synthetic Procedure"],"prefix":"10.3390","volume":"14","author":[{"given":"Jehan Y.","family":"Al-Humaidi","sequence":"first","affiliation":[{"name":"Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. BOX 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed G.","family":"Badrey","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Fayoum University, El-Fayoum 63514, Egypt"},{"name":"Chemistry Department, Faculty of Science and Arts-Almandaq, Al-Baha University, Al-Baha 65515, Saudia Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0314-3408","authenticated-orcid":false,"given":"Ashraf A.","family":"Aly","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Organic Division, Minia University, El-Minia 61519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0531-5194","authenticated-orcid":false,"given":"AbdElAziz A.","family":"Nayl","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, Jouf University, Sakaka 72341, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohie E. M.","family":"Zayed","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ohoud A.","family":"Jefri","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7739-2837","authenticated-orcid":false,"given":"Sobhi M.","family":"Gomha","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt"},{"name":"Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3915","DOI":"10.1007\/s11164-016-2855-6","article-title":"A practical and green protocol for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones using oxalic acid as organocatalyst","volume":"43","author":"Karhale","year":"2017","journal-title":"Res. Chem. Intermed."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.3987\/COM-16-13470","article-title":"DABCO-catalyzed green synthesis of thiazole and 1,3-thiazine derivatives linked to benzofuran","volume":"92","author":"Gomha","year":"2016","journal-title":"Heterocycles"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.ijbiomac.2019.03.019","article-title":"Synthesis, characterization and application of copper oxide chitosan nanocomposite for green regioselective synthesis of [1,2,3]triazoles","volume":"130","author":"Khalil","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1021\/sc400312n","article-title":"Facile and One-Pot Access to Diverse and Densely Functionalized 2-Amino-3-cyano-4H-pyrans and Pyran-Annulated Heterocyclic Scaffolds via an Eco-Friendly Multicomponent Reaction at Room Temperature Using Urea as a Novel Organo-Catalyst","volume":"2","author":"Brahmachari","year":"2014","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"762248","DOI":"10.3389\/fchem.2021.762248","article-title":"Three-component synthesis of some new coumarin derivatives as anti-cancer agents","volume":"9","author":"Alshabanah","year":"2022","journal-title":"Front. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"805","DOI":"10.2174\/1389557516666161223154539","article-title":"Green Synthesis and Molecular Docking of Thiazolyl-thiazole Derivatives as Potential Cytotoxic Agents","volume":"17","author":"Gomha","year":"2017","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1080\/17518253.2019.1710268","article-title":"Green synthesis, molecular docking and anticancer activity of novel 1,4-dihydropyridine-3,5-Dicarbohydrazones under grind-stone chemistry","volume":"13","author":"Gomha","year":"2020","journal-title":"Green Chem. Lett. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.3987\/COM-13-12696","article-title":"A Facile green synthesis and anti-cancer activity of bis-arylhydrazononitriles, triazolo[5,1-c][1,2,4]triazine, and 1,3,4-thiadiazoline","volume":"87","author":"Gomha","year":"2013","journal-title":"Heterocycles"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4359","DOI":"10.1039\/C4GC00676C","article-title":"An environmentally benign, mild, and catalyst-free reaction of quinones with heterocyclic ketene aminals in ethanol: Site-selective synthesis of rarely fused [1,2-a]indolone derivatives via an unexpected anti-Nenitzescu strategy","volume":"16","author":"Zhou","year":"2014","journal-title":"Green Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7561","DOI":"10.1007\/s11164-014-1844-x","article-title":"2-Hydroxy-5-sulfobenzoic acid: An efficient organocatalyst for the three-component synthesis of 1-amidoalkyl-2-naphthols and 3,4-disubstituted isoxazol-5(4H)-ones","volume":"41","author":"Kiyani","year":"2015","journal-title":"Res. Chem. Intermed."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6831","DOI":"10.1007\/s11164-016-2498-7","article-title":"Expeditious Green Synthesis of 3,4-disubstituted isoxazole-5(4H)-ones Catalyzed by Nano-MgO","volume":"42","author":"Kiyani","year":"2016","journal-title":"Res. Chem. Intermed."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1080\/00397911.2017.1399422","article-title":"Novel one-pot expeditious synthesis of 2,4-disubstituted thiazoles through a three-component reaction under solvent free conditions","volume":"48","author":"Sujatha","year":"2018","journal-title":"Synth. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"441","DOI":"10.3906\/kim-1506-13","article-title":"Synthesis and antiviral evaluation of some novel thiazoles and 1,3-thiazines substituted with pyrazole moiety against rabies virus","volume":"40","author":"Abdalla","year":"2016","journal-title":"Turk. J. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.2147\/DDDT.S165276","article-title":"5-(Thiophen-2-yl)-1,3,4-thiadiazole derivatives: Synthesis, molecular docking and in-vitro cytotoxicity evaluation as potential anticancer agents","volume":"12","author":"Gomha","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"215","DOI":"10.2174\/1389557518666180816112151","article-title":"A Review on recent synthetic strategies and pharmacological importance of 1,3-thiazole derivatives","volume":"19","author":"Nayak","year":"2019","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2174\/1570193X15666180412152743","article-title":"Thiazole: A Privileged Motif in Marine Natural Products","volume":"16","author":"Kumar","year":"2019","journal-title":"Mini Rev. Org. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s00706-014-1303-9","article-title":"Synthesis, characterization, and pharmacological evaluation of some novel thiadiazoles and thiazoles incorporating pyrazole moiety as anticancer agents","volume":"146","author":"Gomha","year":"2014","journal-title":"Monatsh. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.taap.2017.06.003","article-title":"Anti-liver cancer activity in vitro and in vivo induced by 2-pyridyl 2, 3-thiazole derivatives","volume":"329","author":"Bomfim","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"280","DOI":"10.2174\/1574892810666150708110432","article-title":"Recent patents on thiazole derivatives endowed with antitumor activity","volume":"10","author":"Morigi","year":"2015","journal-title":"Recent Pat. Anticancer Drug Discov."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Abu-Melha, S., Edrees, M.M., Salem, H.H., Kheder, N.A., Gomha, S.M., and Abdelaziz, M.R. (2019). Synthesis and biological evaluation of some novel thiazole-based heterocycles as potential anticancer and antimicrobial agents. Molecules, 24.","DOI":"10.3390\/molecules24030539"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/BF02524553","article-title":"Adamantane-1- and norbornane-2-carboxylic acid hydrazides as HIV inhibitors","volume":"34","author":"Danilenko","year":"2000","journal-title":"Pharm. Chem. J."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Maniak, H., Talma, M., and Giurg, M. (2021). Inhibitory Potential of New Phenolic Hydrazide-Hydrazones with a Decoy Substrate Fragment towards Laccase from a Phytopathogenic Fungus: SAR and Molecular Docking Studies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212307"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kratky, M., Svrckova, K., Vu, Q.A., Stepankova, S., and Vinsova, J. (2021). Hydrazones of 4-(Trifluoromethyl)benzohydrazide as New Inhibitors of Acetyl- and Butyrylcholinesterase. Molecules, 26.","DOI":"10.3390\/molecules26040989"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Javaid, S., Saad, S.M., Zafar, H., Malik, R., Khan, K.M., Choudhary, M.I., and Rahman, A.-U. (2020). Thymidine phosphorylase and prostrate cancer cell proliferation inhibitory activities of synthetic 4-hydroxybenzohydrazides: In vitro, kinetic, and in silico studies. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0227549"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1039\/B206169B","article-title":"Metrics to \u2018Green\u2019 Chemistry\u2014Which Are the Best?","volume":"4","author":"Constable","year":"2002","journal-title":"Green Chem."},{"key":"ref_26","first-page":"526","article-title":"Development and assessment of green synthesis of hydrazides","volume":"49","author":"Saha","year":"2010","journal-title":"Indian J. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.3389\/fimmu.2020.01638","article-title":"GSK-3 Inhibition as a Therapeutic Approach Against SARs CoV2: Dual Benefit of Inhibiting Viral Replication While Potentiating the Immune 412 Response","volume":"11","author":"Rudd","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","article-title":"A new coronavirus associated with human respiratory disease in China","volume":"579","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.apsb.2020.02.008","article-title":"Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods","volume":"10","author":"Wu","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"E3900","DOI":"10.1073\/pnas.1323705111","article-title":"One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities","volume":"111","author":"Subissi","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"104859","DOI":"10.1016\/j.phrs.2020.104859","article-title":"Candidate drugs against SARS-CoV-2 and COVID-19","volume":"157","author":"McKee","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1177\/095632020601700506","article-title":"Antiviral Activity of Nucleoside Analogues against SARS-coronavirus (SARS-CoV)","volume":"17","author":"Chu","year":"2006","journal-title":"Antivir. Chem. Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.ejmech.2013.08.054","article-title":"2-(2-Hydrazinyl)thiazole derivatives: Design, synthesis and in vitro antimycobacterial studies","volume":"69","author":"Makam","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"eabd4596","DOI":"10.1126\/sciadv.abd4596","article-title":"Activity profiling and crystal structures of inhibitor-bound SARS-CoV-2 papain-like protease: A framework for anti\u2013COVID-19 drug design","volume":"6","author":"Rut","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/nrd1032","article-title":"ADMET in silico modelling: Towards prediction paradise?","volume":"2","author":"Gifford","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1021\/jm020017n","article-title":"Molecular Properties That Influence the Oral Bioavailability of Drug Candidates","volume":"45","author":"Veber","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/j.bmcl.2015.01.041","article-title":"Environmentally benign synthesis, molecular properties prediction and anti-inflammatory activity of novel isoxazolo[5,4-d]isoxazol-3-yl-aryl-methanones via vinylogous Henry nitroaldol adducts as synthons","volume":"25","author":"Rajanarendar","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"355","DOI":"10.2533\/chimia.2007.355","article-title":"Cheminformatic analysis of natural products and their chemical space","volume":"61","author":"Wetzel","year":"2007","journal-title":"CHIMIA Inter. J. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1002\/prot.22896","article-title":"Development of a new physics-based internal coordinate mechanics force field and its application to protein loop modeling","volume":"79","author":"Arnautova","year":"2011","journal-title":"Proteins Struct. Funct. Bioinform."}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/14\/15\/3160\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:01:39Z","timestamp":1760140899000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/14\/15\/3160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,3]]},"references-count":40,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["polym14153160"],"URL":"https:\/\/doi.org\/10.3390\/polym14153160","relation":{},"ISSN":["2073-4360"],"issn-type":[{"value":"2073-4360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,3]]}}}