Synthesis, characterization, antimicrobial activity, and in silico assessment of a novel pyrazoline carboxamide heterocyclic compound

Authors

  • Farouk Boudou Department of Biology, Faculty of Natural and Life Sciences, Djillali Liabes University of Sidi-Bel-Abbes, Sidi-Bel-Abbes 22000, Algeria.
  • Abdelghani Sehmi Department of Natural and Life Sciences, Faculty of Sciences and Technology, University of Tissemsilt, Tissemsilt 38000, Algeria. https://orcid.org/0000-0002-3108-8362
  • Amal Belakredar Department of Biology, Faculty of Natural and Life Sciences, Djillali Liabes University of Sidi-Bel-Abbes, Sidi-Bel-Abbes 22000, Algeria. https://orcid.org/0000-0003-0997-690X
  • Oussama Zaoui Department of Chemistry Faculty of Science, Kasdi Merbah University, BP 511, Ouargla 30000, Algeria. https://orcid.org/0000-0002-5975-2691

DOI:

https://doi.org/10.3329/bjp.v18i4.69267

Keywords:

Pyrazoline Carboxamide, Synthesis, Characterization, Antimicrobial Activity, Druglikeness, Molecular Docking, Molecular Dynamics, Drug Development

Abstract

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

Download data is not yet available.
Abstract
119
Download
191 Supplementary File
151

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.

Published

2023-12-16

How to Cite

Boudou, F., A. . Sehmi, A. Belakredar, and O. . Zaoui. “Synthesis, Characterization, Antimicrobial Activity, and in Silico Assessment of a Novel Pyrazoline Carboxamide Heterocyclic Compound”. Bangladesh Journal of Pharmacology, vol. 18, no. 4, Dec. 2023, pp. 152-61, doi:10.3329/bjp.v18i4.69267.

Issue

Section

Research Articles