Vol.:(0123456789) 1 3 Arabian Journal for Science and Engineering https://doi.org/10.1007/s13369-021-05377-1 RESEARCH ARTICLE-CHEMISTRY Molecular Docking and Antibacterial Studies of Pyranopyrazole Derivatives Synthesized Using [Pap‑Glu@Chi] Biocatalyst Through a Greener Approach Akansha Agrwal 1  · Rajesh Kumar Pathak 2  · Virendra Kasana 3 Received: 5 April 2020 / Accepted: 18 January 2021 © King Fahd University of Petroleum & Minerals 2021 Abstract In the present work, papain enzyme was immobilized on a polymer support chitosan through a linkage of glutaraldehyde to form the [Pap-Glu@Chi] biocatalyst through the covalent bonding method. The immobilization of papain on Chitosan was confrmed by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) which revealed the change in morphology of chitosan due to immobilization of papain through glutaraldehyde. Thus prepared heterogeneous biocatalyst was used for the four-component synthesis of pyranopyrazole derivatives by the reaction of substituted aromatic aldehydes, malononitrile, ethylacetoacetate and hydrazine hydrate afording excellent yields within short reaction times at moderate temperature. The catalyst exhibited signifcant activity up to six cycles. Synthesized compounds were checked for their molecular docking activity using AutoDock Vina against the bacterial protein receptors (PDB code 2VF5 and 1BAG) obtained from the RCSB Protein Data Bank. Signifcant binding energy values obtained from docking studies revealed good interaction between synthesized compounds and bacterial protein receptor. Synthesized compounds were tested against human pathogenic bacterial strains Escherichia coli, Salmonella typhi, Bacillus subtilis, Pseudomonas aeruginosa along with Gentamicine as a reference antibiotic using disk difusion method. The compounds were found to exhibit moderate- to-high antibacterial activity. Keywords [Pap-Glu@Chi] · Biocatalyst · Pyranopyrazole · Chitosan · Multicomponent reaction · Molecular docking · AutoDock Vina 1 Introduction Heterocyclic compounds have been found to exhibit various biological activities. Pyranopyrazoles are an important class of heterocyclic bioactive compounds which are widely used in the feld of medicinal chemistry due to their signifcant antibacterial properties over other heterocyclic compounds [1, 2]. Pyranopyrazole derivatives are found to exhibit antibacterial [2, 3], antioxidant [4], herbicidal [5], antifungal [6], anti-infammatory [7], antiviral [8], anticancer [9] and human Chk1 kinase inhibitor[10] activity. Various catalytic systems such as Ferrite@Silica [11], [bmim][OH − ] [12], iodine [13], cyclodextrin [14], proline [15], triethylamine [16],cinchona alkaloid derivatives [17] and Bronsted-acidic ionic liquid [18] have been developed to improve the synthesis of this biologically important class of compounds. The practice of green chemistry is increas- ing for the search of environmentally friendly catalysts; some of the acceptable alternatives are photocatalysis [19, 20] and use of biocatalysts such as laccase [21], lipase [22, 23], Trypsin [24], β-mannanase [25], Pectin[26] and other enzymes which have been used to catalyze the reactions. Papain is a sustainable and inexpensive biocatalyst which was used frst time to catalyze Knoevenagel reaction[27]. Since then, papain has been used to catalyze a number of reactions [28–30]. Its catalytic promiscuity makes it a good * Akansha Agrwal akansha.agrwal90@gmail.com 1 Department of Chemistry, KIET Group of Institutions, Delhi-NCR, Meerut Road (NH-58), Ghaziabad 201 206, India 2 School of Agricultural Biotechnology, Punjab Agricultural University, Ludhiana, Punjab 141004, India 3 Department of Chemistry, College of Basic Sciences and Humanities, G.B. Pant University of Agriculture and Technology, Pantnagar, India