Unveiling the antimicrobial activity of some new Quinazolindione-anchored Pyrazole, Chromene and/or Furo[2,3-b]indole hybrids through Acylthiourea conjugate: Synthesis, molecular docking, Semiempirical calculations and ADMET prediction
Due to the current need to identify novel and potent drug candidates for treating diseases caused by bacterial and fungal strains. Herein, in this article, our goal is to identify possible potential antimicrobial candidates. The present work includes design and prepare three new series of quinazolin...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-05-01
|
| Series: | Results in Chemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715625001584 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850160313460064256 |
|---|---|
| author | Aboubakr H. Abdelmonsef Amal O.A. Ibrahim Hesham M. Alsoghier Huda R.M. Rashdan Ahmed M. Mosallam Ahmed Khodairy |
| author_facet | Aboubakr H. Abdelmonsef Amal O.A. Ibrahim Hesham M. Alsoghier Huda R.M. Rashdan Ahmed M. Mosallam Ahmed Khodairy |
| author_sort | Aboubakr H. Abdelmonsef |
| collection | DOAJ |
| description | Due to the current need to identify novel and potent drug candidates for treating diseases caused by bacterial and fungal strains. Herein, in this article, our goal is to identify possible potential antimicrobial candidates. The present work includes design and prepare three new series of quinazolindione-based acylthiourea incorporating five and/or six membered rings such as pyrazole, furo[2,3-b]indole and chromene moieties 3–8, in an effort to investigate their potential antimicrobial properties. The starting compound 2 has been synthesized by reaction of benzoyl chloride derivative 1 with cyanoacetic acid hydrazide and ammonium thiocyanate via one pot three components reaction. Additionally, Knӧvenagel condensation of 2 with various heteroaromatic/ aromatic aldehydes and/or aromatic ketone yielded quinazolin-2,4-diones-anchored acylthiourea conjugate with N/O heterocycles 3–8 in good yields ranging from 60 to 75 %. Their chemical structures were authenticated utilizing multispectroscopic techniques such as IR, 1H-& 13C NMR and MS along with the elemental analyses. Further, the antimicrobial potential of the products was in vitro assessed against different bacterial and fungal pathogenic strains. The results revealed that compounds 3b and 3c demonstrated the strongest inhibitory effects against the tested microbial strains at low concentrations. Alongside, virtual screening based on molecular docking studies was further performed on the newly synthesized quinazolin-2,4-diones towards the enzymes Staphylococcus aureus tyrosyl-tRNA synthetase (TyrRS), Pseudomonas aeruginosa lipase enzyme and Candida albicans dihydrofolate reductase (C. albicans DHFR), using ciprofloxacin and nystatin as antibacterial and antifungal standard drugs, respectively. Further, structure activity relationship (SAR) for 3b and 3c was rationalized by investigating the effect of substituents on inhibitory potential. A semiempirical modeling was performed for geometric optimization of the best docked molecules. Our work recommends that compound 3b and 3c could be promising leads for development of potent antimicrobial agents. |
| format | Article |
| id | doaj-art-e27110e6c42e45d694db7d8e69c17796 |
| institution | OA Journals |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj-art-e27110e6c42e45d694db7d8e69c177962025-08-20T02:23:11ZengElsevierResults in Chemistry2211-71562025-05-011510217510.1016/j.rechem.2025.102175Unveiling the antimicrobial activity of some new Quinazolindione-anchored Pyrazole, Chromene and/or Furo[2,3-b]indole hybrids through Acylthiourea conjugate: Synthesis, molecular docking, Semiempirical calculations and ADMET predictionAboubakr H. Abdelmonsef0Amal O.A. Ibrahim1Hesham M. Alsoghier2Huda R.M. Rashdan3Ahmed M. Mosallam4Ahmed Khodairy5Department of Chemistry, Faculty of Science, South Valley University, Qena 83523, Egypt; Corresponding author.Department of Chemistry, Faculty of Science, South Valley University, Qena 83523, EgyptDepartment of Chemistry, Faculty of Science, South Valley University, Qena 83523, EgyptChemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, 33 El Buhouth St, Dokki, Giza 12622, EgyptDepartment of Chemistry, Faculty of Science, South Valley University, Qena 83523, EgyptDepartment of Chemistry, Faculty of Science, Sohag University, Sohag 82524, EgyptDue to the current need to identify novel and potent drug candidates for treating diseases caused by bacterial and fungal strains. Herein, in this article, our goal is to identify possible potential antimicrobial candidates. The present work includes design and prepare three new series of quinazolindione-based acylthiourea incorporating five and/or six membered rings such as pyrazole, furo[2,3-b]indole and chromene moieties 3–8, in an effort to investigate their potential antimicrobial properties. The starting compound 2 has been synthesized by reaction of benzoyl chloride derivative 1 with cyanoacetic acid hydrazide and ammonium thiocyanate via one pot three components reaction. Additionally, Knӧvenagel condensation of 2 with various heteroaromatic/ aromatic aldehydes and/or aromatic ketone yielded quinazolin-2,4-diones-anchored acylthiourea conjugate with N/O heterocycles 3–8 in good yields ranging from 60 to 75 %. Their chemical structures were authenticated utilizing multispectroscopic techniques such as IR, 1H-& 13C NMR and MS along with the elemental analyses. Further, the antimicrobial potential of the products was in vitro assessed against different bacterial and fungal pathogenic strains. The results revealed that compounds 3b and 3c demonstrated the strongest inhibitory effects against the tested microbial strains at low concentrations. Alongside, virtual screening based on molecular docking studies was further performed on the newly synthesized quinazolin-2,4-diones towards the enzymes Staphylococcus aureus tyrosyl-tRNA synthetase (TyrRS), Pseudomonas aeruginosa lipase enzyme and Candida albicans dihydrofolate reductase (C. albicans DHFR), using ciprofloxacin and nystatin as antibacterial and antifungal standard drugs, respectively. Further, structure activity relationship (SAR) for 3b and 3c was rationalized by investigating the effect of substituents on inhibitory potential. A semiempirical modeling was performed for geometric optimization of the best docked molecules. Our work recommends that compound 3b and 3c could be promising leads for development of potent antimicrobial agents.http://www.sciencedirect.com/science/article/pii/S2211715625001584Quinazolin-2,4-dionePyrazoleFuro[2,3-b]indoleChromeneAntimicrobial activityMolecular docking, semiempirical calculations |
| spellingShingle | Aboubakr H. Abdelmonsef Amal O.A. Ibrahim Hesham M. Alsoghier Huda R.M. Rashdan Ahmed M. Mosallam Ahmed Khodairy Unveiling the antimicrobial activity of some new Quinazolindione-anchored Pyrazole, Chromene and/or Furo[2,3-b]indole hybrids through Acylthiourea conjugate: Synthesis, molecular docking, Semiempirical calculations and ADMET prediction Results in Chemistry Quinazolin-2,4-dione Pyrazole Furo[2,3-b]indole Chromene Antimicrobial activity Molecular docking, semiempirical calculations |
| title | Unveiling the antimicrobial activity of some new Quinazolindione-anchored Pyrazole, Chromene and/or Furo[2,3-b]indole hybrids through Acylthiourea conjugate: Synthesis, molecular docking, Semiempirical calculations and ADMET prediction |
| title_full | Unveiling the antimicrobial activity of some new Quinazolindione-anchored Pyrazole, Chromene and/or Furo[2,3-b]indole hybrids through Acylthiourea conjugate: Synthesis, molecular docking, Semiempirical calculations and ADMET prediction |
| title_fullStr | Unveiling the antimicrobial activity of some new Quinazolindione-anchored Pyrazole, Chromene and/or Furo[2,3-b]indole hybrids through Acylthiourea conjugate: Synthesis, molecular docking, Semiempirical calculations and ADMET prediction |
| title_full_unstemmed | Unveiling the antimicrobial activity of some new Quinazolindione-anchored Pyrazole, Chromene and/or Furo[2,3-b]indole hybrids through Acylthiourea conjugate: Synthesis, molecular docking, Semiempirical calculations and ADMET prediction |
| title_short | Unveiling the antimicrobial activity of some new Quinazolindione-anchored Pyrazole, Chromene and/or Furo[2,3-b]indole hybrids through Acylthiourea conjugate: Synthesis, molecular docking, Semiempirical calculations and ADMET prediction |
| title_sort | unveiling the antimicrobial activity of some new quinazolindione anchored pyrazole chromene and or furo 2 3 b indole hybrids through acylthiourea conjugate synthesis molecular docking semiempirical calculations and admet prediction |
| topic | Quinazolin-2,4-dione Pyrazole Furo[2,3-b]indole Chromene Antimicrobial activity Molecular docking, semiempirical calculations |
| url | http://www.sciencedirect.com/science/article/pii/S2211715625001584 |
| work_keys_str_mv | AT aboubakrhabdelmonsef unveilingtheantimicrobialactivityofsomenewquinazolindioneanchoredpyrazolechromeneandorfuro23bindolehybridsthroughacylthioureaconjugatesynthesismoleculardockingsemiempiricalcalculationsandadmetprediction AT amaloaibrahim unveilingtheantimicrobialactivityofsomenewquinazolindioneanchoredpyrazolechromeneandorfuro23bindolehybridsthroughacylthioureaconjugatesynthesismoleculardockingsemiempiricalcalculationsandadmetprediction AT heshammalsoghier unveilingtheantimicrobialactivityofsomenewquinazolindioneanchoredpyrazolechromeneandorfuro23bindolehybridsthroughacylthioureaconjugatesynthesismoleculardockingsemiempiricalcalculationsandadmetprediction AT hudarmrashdan unveilingtheantimicrobialactivityofsomenewquinazolindioneanchoredpyrazolechromeneandorfuro23bindolehybridsthroughacylthioureaconjugatesynthesismoleculardockingsemiempiricalcalculationsandadmetprediction AT ahmedmmosallam unveilingtheantimicrobialactivityofsomenewquinazolindioneanchoredpyrazolechromeneandorfuro23bindolehybridsthroughacylthioureaconjugatesynthesismoleculardockingsemiempiricalcalculationsandadmetprediction AT ahmedkhodairy unveilingtheantimicrobialactivityofsomenewquinazolindioneanchoredpyrazolechromeneandorfuro23bindolehybridsthroughacylthioureaconjugatesynthesismoleculardockingsemiempiricalcalculationsandadmetprediction |