How to cite this paper
Hamed, M., Ahmed, M., El-Dean, A., Alsedfy, M & Tolba, M. (2025). Thiopental-Inspired alkylpyrimidines as dual-target antimicrobial agents: Synthesis, biological activity, and molecular docking validation.Current Chemistry Letters, 14(4), 831-842.
Refrences
[1] Koubi Y., Moukhliss Y., Hajji H., Abdessadak O., Alaqarbeh M., Ajana M. A., Maghat H., Lakhlifi T., and Bouachrine M. (2024) Computational structure–biological activity and retrosynthesis investigations of 1,2,3-triazole-quinoline hybrid molecules as potential respiratory virus inhibitors. Chem. Heterocycl. Compd., 60 (9/10) 491-504.
[2] Wei J., Chen L., Zhu K., Cheng Y. X., and Huang D. (2024) Design, synthesis, and fungicidal activity evaluation of 2-methyl-5-phenylthiazole-4-carboxamides bearing morpholine, thiomorpholine, or thiomorpholine 1,1-dioxide moiety. Chem. Heterocycl. Compd., 60 (9/10) 536-543.
[3] Molchanova M. V., Ikonnikova V. A., Anisenko A. N., Gottikh M. B., Baranov M. S., and Mikhaylov A. A. (2024) The cycloaddition reaction of benzothiazolium ylides with α-cyanocinnamamides: the synthesis of structural analogs of inhibitors of HIV-1 post-integrational repair. Chem. Heterocycl. Compd., 60 (9/10) 544-548.
[4] Mohamed S. K., Mague J. T., Akkurt M., Alfayomy A. M., Abou Seri S. M., Abdel-Raheem Sh. A. A., and Abdul-Malik M. A. (2022) Crystal structure and Hirshfeld surface analysis of ethyl (3E)-5-(4-chlorophenyl)-3-{[(4-chlorophenyl)formamido]imino}-7-methyl-2H,3H,5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate. Acta Cryst., 78 (8) 846-850.
[5] Abdel-Raheem Sh. A. A., Drar A. M., Hussein B. R. M., and Moustafa A. H. (2023) Some oxoimidazolidine and cyanoguanidine compounds: Toxicological efficacy and structure-activity relationships studies. Curr. Chem. Lett., 12 (4) 695–704.
[6] El Bakri Y., Mohamed S. K., Saravanan K., Ahmad S., Mahmoud A. A., Abdel-Raheem Sh. A. A., ElSayed W. M., Mague J. T., and Said S. G. (2023) 1,4,9,9-tetramethyloctahydro-4,7-(epoxymethano)azulen-5(1H)-one, a natural product as a potential inhibitor of COVID-19: Extraction, crystal structure, and virtual screening approach. J. King Saud Univ. Sci., 35 (4) 102628.
[7] Abdelhamid A. A., Elsaghier A. M. M., Aref S. A., Gad M. A., Ahmed N. A., and Abdel-Raheem Sh. A. A. (2021) Preparation and biological activity evaluation of some benzoylthiourea and benzoylurea compounds. Curr. Chem. Lett., 10 (4) 371-376.
[8] Fouad M. R., Shamsan A. Q. S., and Abdel-Raheem Sh. A. A. (2023) Toxicity of atrazine and metribuzin herbicides on earthworms (Aporrectodea caliginosa) by filter paper contact and soil mixing techniques. Curr. Chem. Lett., 12 (1) 185–192.
[9] Fouad M. R., and Abdel-Raheem Sh. A. A. (2024) An overview on the fate and behavior of imidacloprid in agricultural environments. Environ. Sci. Pollut. Res., 31 61345-61355.
[10] Ibrahim S. M., Abdelkhalek A. S., Abdel-Raheem Sh. A. A., Freah N. E., El Hady N. H., Aidia N. K., Tawfeq N. A., Gomaa N. I., Fouad N. M., Salem H. A., Ibrahim H. M., and Sebaiy M. M. (2024) An overview on 2-indolinone derivatives as anticancer agents. Curr. Chem. Lett., 13 (1) 241-254.
[11] Mohamed S. K.; Mague J. T.; Akkurt M.; Alfayomy A. M.; Ragab F. A., and Abd ul-Malik M. A. (2022) Crystal structure and Hirshfeld surface analysis of ethyl (3E)-5-(4-fluorophenyl)3-{[(4-methoxyphenyl)formamido]imino}-7-methyl-2H,3H,5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate 0.25-hydrate. Acta Cryst., 78 (9) 880-884.
[12] Abd ul‐Malik M. A.; Kamal El‐Dean A. M.; Radwan S. M.; and Zaki R. M. (2021) Facile synthesis and antimicrobial evaluations of some novel pyrazolo[3,4‐b]selenolo[3,2‐e]pyrazines and their related heterocycles. J. Heterocycl. Chem., 58 (11) 2067-2077.
[13] Zaki R. M., Kamal El‐Dean A. M., Radwan S. M., and Abdul‐Malik M. A. (2020) Efficient synthesis, reactions, and biological activities of new thieno and furopyrazolo[3,4‐b]pyrazines and their related heterocycles. J. Chin. Chem. Soc., 67 (4) 658-673.
[14] Alshera`a A. A., Hussein A. M., Kamal El-Dean A. M., Thabet E. A., Abdul-Malik M. A., Gad M. A., Qaid F. M. Q., Abdelkhalek A. S., and Abdel-Raheem Sh. A. A. (2025) Chemical design, preparation, agricultural bioefficacy valuation, and molecular docking of some pyridine containing compounds, Curr. Chem. Lett., 14 (3) 407-416.
[15] Abd-Ella A. A., Metwally S. A., Abdul-Malik M. A., El-Ossaily Y. A., AbdElrazek F. M., Aref S. A., Naffea Y. A., and Abdel-Raheem Sh. A. A. (2022) A review on recent advances for the synthesis of bioactive pyrazolinone and pyrazolidinedione derivatives. Curr. Chem. Lett., 11 (2) 157-172.
[16] Sebaiy M. M., El-Adl S. M., Nafea A., Mattar A. A., Abdul-Malik M. A., Abdel-Raheem Sh. A. A., and Elbaramawi S. S. (2024) Review: Instrumental Analytical techniques for Evaluating some Anti-infective Drugs in Pharmaceutical Products and Biological Fluids. Curr. Chem. Lett., 13 491-502.
[17] Abdelkhalek A. S., Abokull M. E., Ibrahim S. M., Soltan M. K., Abdul-Malik M. A., and Abdel-Raheem Sh. A. A. (2024) A review on some synthetic methods of 4(3H)-quinazolinone and benzotriazepine derivatives and their biological activities. Org.Commun., 17 63−98.
[18] Sebaiy M. M., El-Adl S. M., Elbaramawi S. S., Abdel-Raheem Sh. A. A., and Nafie A. (2024) Developing a highly validated and sensitive HPLC method for simultaneous estimation of cefotaxime and paracetamol in pure and pharmaceutical preparations.Curr. Chem. Lett., 13 435-444.
[19] El-Ossaily Y. A., Alanazi N. M. M., Althobaiti I. O., Altaleb H. A., Al-Muailkel N. S., El-Sayed M. Y., Hussein M. F., Ahmed I. M., Alanazi M. M., Fawzy A., Abdel-Raheem Sh. A. A., and Tolba M. S. (2024) Multicomponent Approach to the Synthesis and Spectral Characterization of Some 3,5-Pyrazolididione Derivatives and Evaluation as Anti-inflammatory Agents. Curr. Chem. Lett., 13 (1) 127-140.
[20] Abdul-Malik M. A., Abdou A., Fouad M. R., Alkamali A. S. N., and Abdel-Raheem Sh. A. A. (2024) Synthesis, spectral characterization and molecular docking studies of some thiocarbohydrazide-based Schiff bases with pyrazole moiety as potential anti-inflammatory agents. Curr. Chem. Lett., 13 683–694.
[21] Gad M. A., Aref S. A., Abdelhamid A. A., Elwassimy M. M., and Abdel-Raheem Sh. A. A. (2021) Biologically active organic compounds as insect growth regulators (IGRs): introduction, mode of action, and some synthetic methods. Curr. Chem. Lett., 10 (4) 393-412.
[22] Elhady O. M., Mansour E. S., Elwassimy M. M., Zawam S. A., Drar A. M., and Abdel-Raheem Sh. A. A. (2022) Selective synthesis, characterization, and toxicological activity screening of some furan compounds as pesticidal agents. Curr. Chem. Lett., 11 (3) 285-290.
[23] Hussein B. R. M., Moustafa A. H., Abdou A.; Drar A. M., and Abdel-Raheem Sh. A. A. (2024) Preparation, agricultural bioactivity evaluation, structure-activity relationships estimation, and molecular docking of some quinazoline compounds. J. Agric. Food Chem., 72 8973–8982.
[24] Abdel-Raheem Sh. A. A., Kamal El-Dean A. M., Zaki R. M., Hassanien R., El-Sayed M. E. A., Sayed M., and Abd-Ella A. A. (2021) Synthesis and toxicological studies on distyryl-substituted heterocyclic insecticides. Eur. Chem. Bull., 10 (4) 225-229.
[25] Abdel-Raheem Sh. A. A., Kamal El-Dean A. M., Abdul-Malik M. A., Hassanien R., El-Sayed M. E. A., Abd-Ella A. A., Zawam S. A., and Tolba M. S. (2022) Synthesis of new distyrylpyridine analogues bearing amide substructure as effective insecticidal agents. Curr. Chem. Lett., 11 (1) 23-28.
[26] Tolba M. S., Abdul-Malik M. A., Kamal El-Dean A. M., Geies A. A., Radwan Sh. M., Zaki R. M., Sayed M., Mohamed S. K., and Abdel-Raheem Sh. A. A. (2022) An overview on synthesis and reactions of coumarin based compounds. Curr. Chem. Lett., 11 (1) 29-42.
[27] Abdel-Raheem Sh. A. A., Kamal El-Dean A. M., Hassanien R., El-Sayed M. E. A., and Abd-Ella A. A. (2021) Synthesis and characterization of some distyryl-derivatives for agricultural uses. Eur. Chem. Bull., 10 (1) 35-38.
[28] Kamal El-Dean A. M., Abd-Ella A. A., Hassanien R., El-Sayed M. E. A., and Abdel-Raheem Sh. A. A. (2019) Design, Synthesis, Characterization, and Insecticidal Bioefficacy Screening of Some New Pyridine Derivatives. ACS Omega, 4 (5) 8406-8412.
[29] Abdel-Raheem Sh. A. A., Kamal El-Dean A. M., Hassanien R., El-Sayed M. E. A., Sayed M., and Abd-Ella A. A. (2021) Synthesis and spectral characterization of selective pyridine compounds as bioactive agents. Curr. Chem. Lett., 10 (3) 255-260.
[30] Kamal El-Dean A. M., Abd-Ella A. A., Hassanien R., El-Sayed M. E. A., Zaki R. M., and Abdel-Raheem Sh. A. A. (2019) Chemical design and toxicity evaluation of new pyrimidothienotetrahydroisoquinolines as potential insecticidal agents. Toxicol. Rep., 6 (2019) 100-104.
[31] Abdul‐Malik M. A., Zaki R. M., Kamal El‐Dean A. M., and Radwan S. M. A (2018) concise review on the synthesis and reactions of pyrazolopyrazine heterocycles. J. Heterocycl. Chem., 55 (8) 1828-1853.
[32] Zaki R. M., El‐Dean A. M., Radwan S. M., Abdul‐Malik M. A. (2018) A facile synthesis, reactions, and spectral characterization of some novel thieno[3,2‐e]pyrazolo[3,4‐b]pyrazine compounds. J. Chin. Chem. Soc., 65 (11) 1407-1414.
[33] Kamal El-Dean A. M.; Radwan S. M.; Zaki R. M.; and Abd ul-Malik M. A. (2018) Efficient synthesis of some novel furo[3,2-e]pyrazolo[3,4-b]pyrazines and related heterocycles. Synth. Commun., 48 (4) 395-412.
[34] Abdel-Raheem Sh. A. A., Kamal El-Dean A. M., Abdul-Malik M. A., Marae I. S., Bakhite E. A., Hassanien R., El-Sayed M. E. A., Zaki R. M., Tolba M. S., Sayed A. S. A., and Abd-Ella A. A. (2022) Facile synthesis and pesticidal activity of substituted heterocyclic pyridine compounds. Rev. Roum. Chem., 67 (4-5) 305-309.
[35] Abdelkhalek A. S., Abdulrahman A., Abokull M. E., Ibrahim S. M., Soltan M. K., Abdul-Malik M. A., and Abdel-Raheem Sh. A. A. (2025) An overview of pyrazolo[3,4-d]pyrimidine heterocycles: recent synthetic approaches and biological activities. J. Indian Chem. Soc., 102 (7) 101763.
[36] Tolba M. S., Kamal El-Dean A. M., Ahmed M., Hassanien R., Sayed M., Zaki R. M., Mohamed S. K., Zawam S. A., and Abdel-Raheem Sh. A. A. (2022) Synthesis, reactions, and applications of pyrimidine derivatives. Curr. Chem. Lett., 11 (1) 121-138.
[37] Tolba M. S., Sayed M., Abdel-Raheem Sh. A. A., Gaber T. A., Kamal El-Dean A. M., and Ahmed M. (2021) Synthesis and spectral characterization of some new thiazolopyrimidine derivatives. Curr. Chem. Lett., 10 (4) 471-478.
[38] Drar A. M., Abdel-Raheem Sh. A. A., Moustafa A. H., and Hussein B. R. M. (2023) Studying the toxicity and structure-activity relationships of some synthesized polyfunctionalized pyrimidine compounds as potential insecticides. Curr. Chem. Lett., 12 (3) 499-508.
[39] Tolba M. S., Sayed M., Kamal El-Dean A. M., Hassanien R., Abdel-Raheem Sh. A. A., and Ahmed M. (2021) Design, synthesis and antimicrobial screening of some new thienopyrimidines. Org. Commun., 14 (4) 365−376.
[40] Manna T., Maji S., Maity M., Debnath B., Panda S., Khan S. A., Nath R., and Akhtar M. J. (2025) Anticancer potential and structure activity studies of purine and pyrimidine derivatives: an updated review. Mol. Divers., 29 (1) 817-848.
[41] Lagoja I. M. (2005) Pyrimidine as constituent of natural biologically active compounds. Chem. Biodivers., 2 (1) 1-50.
[42] Bushby S. R., and Hitchings G. H. (1968) Trimethoprim, a sulphonamide potentiator. Br. J. Pharmac. Chemother., 33 (1) 72-90.
[43] Capdeville R., Buchdunger E., Zimmermann J., and Matter A. (2002) Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nat. Rev. Drug Discov., 1 (7) 493-502.
[44] Elkhalifa D., Siddique A. B., Qusa M., Cyprian F. S., El Sayed K., Alali F., Al Moustafa A., and Khalil A. (2020) Design, synthesis, and validation of novel nitrogen-based chalcone analogs against triple negative breast cancer. Eur. J. Med. Chem., 187 111954.
[45] Kumar G., and Singh N. P. (2021) Synthesis, anti-inflammatory and analgesic evaluation of thiazole/oxazole substituted benzothiazole derivatives. Bioorg. Chem., 107 104608.
[46] Jiang X., Yu J., Zhou Z., Kongsted J., Song Y., Pannecouque C., Clercq E. D., Kang D., Poongavanam V., Liu X., and Zhan P. (2019) Molecular design opportunities presented by solvent‐exposed regions of target proteins. Med. Res. Rev., 39 (6) 2194-2238.
[47] Rashid S., Yoshigoe Y., and Saito S. (2022) Phenanthroline based rotaxanes: recent developments in syntheses and applications. RSC Adv., 12 (18) 11318-11344.
[48] Scott M., and McCluggage W. G. (2003) Ovarian Cancer: Jacobs IJ, Shepherd JH, Oram DH, et al, eds.(£ 125.00.) Oxford University Press, 2002. ISBN 0 19850826 3.
[49] Jeschke P. (2017) Latest generation of halogen‐containing pesticides. Pest Manag. Sci., 73 (6) 1053-1066.
[50] Abdel-Raheem Sh. A. A., Fouad M. R., Gad M. A., Kamal El-Dean A. M., and Tolba M. S. (2023) Environmentally Green Synthesis and Characterization of Some Novel Bioactive Pyrimidines with Excellent Bioefficacy and Safety Profile Towards Soil Organisms. J. Environ. Chem. Eng., 11 (5) 110839.
[51] Wong W. Y., and Ho C. L. (2009) Heavy metal organometallic electrophosphors derived from multi-component chromophores. Coord. Chem. Rev., 253 (13-14) 1709-1758.
[52] Franks N. P., and Lieb W. R. (1994) Molecular and cellular mechanisms of general anaesthesia. Nature, 367 (6464) 607-614.
[53] Osterblad M., Leistevuo J., Leistevuo T., Järvinen H., Pyy L., Tenovuo J., and Huovinen P. (1995) Antimicrobial and mercury resistance in aerobic gram-negative bacilli in fecal flora among persons with and without dental amalgam fillings. Antimicrob. Agents Chemother., 39 (11) 2499-2502.
[54] Alberti M. O., Hindler J. A., and Humphries R. M. (2016) Erratum for Alberti et al., Antimicrobial Susceptibilities of Abiotrophia defectiva, Granulicatella adiacens, and Granulicatella elegans. Antimicrob. Agents Chemother., 60 (6) 3868-3868.
[55] Sayiprathap B. R., Patibanda A. K., Prasanna Kumari V., Jayalalitha K., Ramappa H. K., Rajeswari E., Karthiba L., Saratbabu K., Sharma M., and Sudini H. K. (2022) Salient findings on host range, resistance screening, and molecular studies on sterility mosaic disease of pigeonpea induced by Pigeonpea sterility mosaic viruses (PPSMV-I and PPSMV-II). Front. Microbiol., 13 838047.
[56] Volkova T. V., and Perlovich G. L. (2020) Comparative analysis of solubilization and complexation characteristics for new antifungal compound with cyclodextrins. Impact of cyclodextrins on distribution process. Eur. J. Pharm. Sci., 154 105531.
[57] Fair R. J., and Tor Y. (2014) Antibiotics and bacterial resistance in the 21st century. Perspect. Med. Chem., 6 25-64.
[58] Tolba M. S., Ahmed M., Mohammed A. A., Saddik A. A., Sayed M., Hassanien R., Kamal El-Dean A. M., Hassan A., and Younis O. (2025) Synthesis, photoluminescence, antimicrobial evaluation, molecular docking, and pharmacokinetic prediction of new pyrimidoselenolo[2,3-d]pyrimidine derivatives. J. Mol. Struct., 1336 142097.
[59] Ahmed M., Hamed M. M., Sayed M., El-Rashedy A. A., El-Dean A. M. K., Hassan M. H., Mady M. F., and Tolba M. S. (2025) Synthesis, antimicrobial activity, molecular docking and molecular dynamics studies of novel bioactive compounds derived from propylthiouracil. J. Mol. Struct., 1333 141779.
[60] Hamed M. M., Ahmed M., Kamal El-Dean A. M., Hassan M. H., and Tolba M. S. (2025) Propylthiouracil Derivatives: Synthesis and Evaluation of Antimicrobial Efficacy Against Pathogenic Strains. New Valley University Journal of Basic and Applied Sciences (NUJBAS), 3 (1) 1-9.
[61] Ahadi S., Abaszadeh M., Khavasi H. R., and Bazgir A. (2012) An efficient three-component synthesis of new barbiturate salts. Tetrahedron, 68 (13) 2906-2916.
[62] Alsedfy M. Y., Ebnalwaled A. A., Moustafa M., and Said A. H. (2024) Investigating the binding affinity, molecular dynamics, and ADMET properties of curcumin-IONPs as a mucoadhesive bioavailable oral treatment for iron deficiency anemia. Sci. Rep., 14 (1) 22027.
[63] Shivanika C., Kumar D., Ragunathan V., Tiwari P., and Sumitha A. (2020) Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease. J. Biomol. Struct. Dyn., 40 (2) 585-611.
[64] Bertonha A. F., Silva C. C., Shirakawa K. T., Trindade D. M., and Dessen A. (2023) Penicillin-binding protein (PBP) inhibitor development: A 10-year chemical perspective. Exp. Biol. Med., 248 (19) 1657-1670.
[65] Mora-Ochomogo M., and Lohans C. T. (2021) β-Lactam antibiotic targets and resistance mechanisms: from covalent inhibitors to substrates. RSC Med. Chem., 12 (10) 1623-1639.
[66] Sulistyowaty, M. I., Putra, G. S., Budiati, T., Indrianingsih, A. W., Anwari, F., Kesuma, D., Matsunami, K., & Yamauchi, T. (2023). Synthesis, In Silico Study, Antibacterial and Antifungal Activities of N-phenylbenzamides. International Journal of Molecular Sciences., 24(3), 2745.
[67] Guengerich F. P. (2024) Cytochrome P450 enzymes as drug targets in human disease. Drug Metab Dispos., 52 (6) 493-497.
[68] Newsome A. W., Nelson D., Corran A., Kelly S. L., and Kelly D. E. (2013) The cytochrome P 450 complement (CYPome) of Mycosphaerella graminicola. Biotechnol. Appl. Biochem., 60 (1) 52-64.
[69] Sadowski E., Pietrancosta N., Veyron-Churlet R., Boucher J.L., Pionneau C., Clodic G., Matheron L., Poch O., Mayer C., Sachon E., Aubry A.(2025) Characterization of the Orphan Cytochrome P450 CYP135B1 from Mycobacterium tuberculosis: Involvement in Metabolism but Not in the Antibacterial Activity of the Antitubercular Drug SQ109.ACS Infectious Diseases.,11 (4), 869-881.
[70] Balding P. R., Porro C. S., McLean K. J., Sutcliffe M. J., Marechal J. D., Munro A. W., and Visser S. P. D. (2008) How do azoles inhibit cytochrome P450 enzymes? A density functional study. J. Phys. Chem. A., 112 (50) 12911-12918.
[71] Wang, N., Liu, Y., Jiang, Z., Chen, L., & Liang, X. (2025). Evaluation of the safety of fenbuconazole monomers via enantioselective toxicokinetics, molecular docking and enantiomer conversion analyses. Journal of Agricultural and Food Chemistry, 73(16), 9894–9905.