Synthesis, characterization, antimicrobial activity, and in silico assessment of a novel pyrazoline carboxamide heterocyclic compound
DOI:
https://doi.org/10.3329/bjp.v18i4.69267Keywords:
Pyrazoline Carboxamide, Synthesis, Characterization, Antimicrobial Activity, Druglikeness, Molecular Docking, Molecular Dynamics, Drug DevelopmentAbstract
This study presents the synthesis, characterization, and antimicrobial efficacy of a novel pyrazoline carboxamide heterocyclic compound. Synthesized through a two-step process, involving the formation of an α,β-unsaturated ketone and subsequent conversion into a pyrazoline carboxamide derivative, the compound's structure and functional groups were confirmed using FT-IR, 1H NMR, and DEPT-135 techniques. The compound demonstrated high purity and yield, displaying significant inhibitory zones against micro-organisms, notably Listeria monocytogenes (14.2 ± 0.0 mm to 16.8 ± 1.3 mm) and Candida albicans (10.9 ± 0.6 mm to 17.8 ± 1.5 mm). Evaluation of drug-likeness and toxicity highlighted its potential for drug development. Molecular dock-ing studies indicated strong binding affinities to key antimicrobial target proteins, including DNA gyrase, penicillin-binding protein, and C. albicans sterol 14-α-demethylase. Molecular dynamics simulations revealed the com-pound's structural flexibility. These results make this new compound a candidate for further exploration in drug development, highlighting its potential therapeutic applications.
Downloads
5
3 Supplementary File
2
References
Abdelli I, Hassani F, Bekkel Brikci S, Ghalem S. In silico study the inhibition of angiotensin converting enzyme 2 receptor of COVID-19 by Ammoides verticillata components harvested from Western Algeria. J Biomol Struct Dyn. 2021; 39: 3263-76.
Ahmad I, Khan H, Serdaroğlu G. Physicochemical properties, drug likeness, ADMET, DFT studies, and in vitro antioxidant activity of oxindole derivatives. Comput Biol Chem. 2023; 104: 107861-80.
Aslam B, Wang W, Arshad MI, Khurshid M, Muzammil S, Rasool MH, Nisar MA, Alvi RF, Aslam MA, Qamar MU. Antibiotic resistance: A rundown of a global crisis. Infect Drug Resist. 2018; 11: 1645-58.
Baell JB, Holloway GA. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J Med Chem. 2010; 53: 2719-40.
Burke A, Di Filippo M, Spiccio S, Schito AM, Caviglia D, Brullo C, Baumann M. Antimicrobial evaluation of new pyrazoles, indazoles and pyrazolines prepared in continuous flow mode. Int J Mol Sci. 2023; 24: 5319-31.
Chen H, Bajorath J. Designing highly potent compounds using a chemical language model. Sci Rep. 2023; 13: 7412-23.
Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017; 7: 42717.
Daisley B, Koenig AD, Engelbrecht K, Doney L, Hards K, Al KF, Reid G, Burton JP. Emerging connections between gut microbiome bioenergetics and chronic metabolic diseases. Cell Rep. 2021; 37: 110087-106.
Ebenezer O, Shapi M, Tuszynski JA. A review of the recent development in the synthesis and biological evaluations of pyrazole derivatives. Biomedicines 2022; 10: 1124-81.
Ignatov I. Antimicrobial activity of colloidal nanosilver 24 ppm in vitro. Bulg Chem Commun. 2021; 53: 365-70.
Ji C, Svensson F, Zoufir A, Bender A. eMolTox: Prediction of molecular toxicity with confidence. Bioinformatics 2018; 34: 2508-09.
Kleandrova VV, Speck-Planche A. The QSAR paradigm in fragment-based drug discovery: From the virtual generation of target inhibitors to multi-scale modeling. Mini Rev Med Chem. 2020; 20: 1357-74.
Kumar K, Anbarasu A, Ramaiah S. Molecular docking and molecular dynamics studies on β-lactamases and penicillin binding proteins. Mol Biosyst. 2014; 10: 891-900.
Lake KM, Rankin SC, Rosenkrantz WS, Sastry L, Jacob M, Campos DD, Maddock K, Cole SD. In vitro efficacy of 0.2% and 0.4% sodium oxychlorosene against meticillin‐resistant Staphylococcus pseudintermedius. Vet Dermatol. 2023; 34: 33-39.
Li B, Webster TJ. Bacteria antibiotic resistance: New challenges and opportunities for implant‐associated orthopedic infections. J Orthop Res. 2018; 36: 22-32.
Lipinski B. Pathophysiology of oxidative stress in diabetes mellitus. J Diabetes Complicat. 2021; 15: 203-10.
Liu Z. Principal component analysis and normal mode analysis of elastic network models and their applications to myosin motor proteins. Doctoral dissertation. Wayne State University. 2022, pp 2023.
López-Blanco JR, Aliaga JI, Quintana-Ortí ES. Chacón P. iMODS: Internal coordinates normal mode analysis server. Nucleic Acids Res. 2014; 42(W1): W271-76.
May A, Zacharias M. Energy minimization in low‐frequency normal modes to efficiently allow for global flexibility during systematic protein–protein docking. Proteins: Struct Funct Bioinf. 2008; 70: 794-809.
Mishra SK, Jernigan RL. Protein dynamic communities from elastic network models align closely to the communities defined by molecular dynamics. PLoS One. 2018; 13: e0199225.
Pardridge WM. Drug transport across the blood–brain barrier. J Cereb blood flow Metab. 2012; 32: 1959-72.
Quezada AG, Díaz-Salazar AJ, Cabrera N, Perez-Montfort R, Pineiro A, Costas M. Interplay between protein thermal flexibility and kinetic stability. Structure 2017; 25: 167-79.
Rani M, Yusuf M, Khan SA. Synthesis and in-vitro-antibacterial activity of [5-(furan-2-yl)-phenyl]-4,5-carbothioamide-pyrazolines. J Saudi Chem Soc. 2012; 16: 431-36.
Rattanasuk S, Boongapim R, Phiwthong T. Antibacterial activity of Cathormion umbellatum. Bangladesh J Pharmacol. 2021; 16: 91-95.
Rossiter SE, Fletcher MH, Wuest WM. Natural products as platforms to overcome antibiotic resistance. Chem Rev. 2017; 117: 12415-74.
Sehmi A, Ouici H, Guendouzi A, Ferhat M, Benali O, Boudjellal FJJS. Corrosion inhibition of mild steel by newly synthesized pyrazole carboxamide derivatives in HCl acid medium: Experimental and theoretical studies. J Electrochem Soc. 2020; 167: 155508-27.
Sumera F, Anwer M, Waseem A, Fatima N, Malik A, Ali, Zahid A. Molecular docking and molecular dynamics studies reveal secretory proteins as novel targets of temozolomide in glioblastoma multiforme. Molecules 2022; 27: 7198-214.
Sun Z, Liu Q, Qu G, Feng Y, Reetz MT. Utility of B-factors in protein science: Interpreting rigidity, flexibility, and internal motion and engineering thermostability. Chem. Rev. 2019; 119: 1626-65.
Sundar RDV, Arunachalam S. Effect of endophytic fungi Daldinia eschscholtzii against multidrug resistant pathogens. Bangladesh J Pharmacol. 2023; 18: 17-23.
Szczepankiewicz F, van Westen D, Englund E, Westin CF, Ståhlberg J, Lätt PC. Sundgren and M. Nilsson. The link between diffusion MRI and tumor heterogeneity: Mapping cell eccentricity and density by diffusional variance decomposition (DIVIDE). Neuroimage 2016; 142: 522-32.
Trott O, Olson AJ. AutoDock vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010; 31: 455-61.
Venkataraman S, Jain S, Shah K, Upmanyu N. Synthe-sis and biological activity of some novel pyrazolines. Acta Pol Pharm. 2010; 67: 361-66.
Vică ML, Glevitzky M, Tit DM, Behl T, Heghedűş-Mîndru RC, Zaha DC, Ursu F, Popa M, Glevitzky I, Bungău S. The antimicrobial activity of honey and propolis extracts from the central region of Romania. 2021; Food Biosci. 41: 101-14.
Wan‐Mohtar WAAQI, Ibrahim MF, Rasdi NW, Zainorahim N,Taufek NM. Microorganisms as a sustainable aquafeed ingredient: A review. Aquac. Res. 2022; 53: 746-66.
Zelelew D, Endale M, Melaku Y, Kedir F, Demissie TB, Ombito JO, Eswaramoorthy R. Synthesis, antibacterial, and antioxidant activities of thiazolylpyrazoline schiff base hybrids: A combined experimental and computational study. J Chem. 2022; 2022.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Farouk Boudou, Abdelghani Sehmi, Amal Belakredar, Oussama Zaoui
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
