Pyrazole Analogues Research Articles

Integrated computational approaches for identification of potent pyrazole-based glycogen synthase kinase-3β (GSK-3β) inhibitors: 3D-QSAR, virtual screening, docking, MM/GBSA, EC, MD simulation studies.

Glycogen synthase kinase-3β (GSK-3β) has emerged as a crucial target due to its substantial contribution in various cellular processes. Dysfunctional GSK-3β activity can lead to ion channel disturbances, sustain abnormal excitability, and contribute to the pathogenesis of epilepsy and other GSK-3β-related disorders. A set of 82 pyrazole analogs was utilized to study its structural features using a three-dimensional quantitative structure-activity relationship (3D-QSAR), virtual screening, molecular docking, and molecular dynamics. The QSAR model, validated using internal and external methods, demonstrated robustness with a high correlation coefficient r2training = 0.99, cross-validation coefficient q2 = 0.79, r2test = 0.69, and r2external = 0.74. The "Average of Actives" in the Activity Atlas model identified 17 molecules as active. Subsequent pharmacophore-based virtual screening of 17 actives yielded 70 compounds, which were selected as the prediction set to determine the potential GSK-3β inhibitors. Docking studies pinpointed compound P66 as the promising lead compound, with a docking score of - 10.555kcal/mol. These findings were further supported by electrostatic potential (ESP), electrostatic complementarity (EC), and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) analyses. Furthermore, a 500ns molecular dynamics (MD) simulation confirmed the structural and conformational stability of the lead complex throughout the simulation period. As a result, this study suggests that compound P66 holds the potential to be a potent lead candidate for the inhibition of GSK-3β, offering a novel therapeutic approach for GSK-3β related disorders, including epilepsy.

Studi Molecular Docking dan Evaluasi Farmakokinetik Senyawa Analog Pirazol Turunan Benzen-Sulfonilurea sebagai Inhibitor Enzim Aldose Reduktase and α-Glukosidase Menggunakan Pendekatan In Silico

The pyrazole scaffold modification in various chemical structures on several studies has shown various biopharmacological activities. This study aims to predict the potential inhibition of pyrazole analogs derived benzene-sulfonylurea (4A, 4B, 4E, 5A, 5C, 5D) against the α-glucosidase (3A4A) and aldose reductase (3RX2) enzymes based on a molecular docking approach using Molecular Operating Environment (MOE) 2020.0102 software and evaluate pharmacokinetic profile (ADMET). In this study, the six test compounds were obtained from previous studies that have been proven antihyperglycemic. The results showed that all the 3,5-disubstituted benzene-sulfonylurea derivative pyrazole analogs are predicted to have low inhibitory activity against the α-glucosidase enzyme. Further, all compounds showed good aldose reductase inhibitor activity and had lower binding free energy values ​​than tolrestat as the positive control (-6.82 kcal/mol). Compound 5C has the best potential inhibitory activity against the aldose reductase enzyme compared to the other test compounds, because it has the lowest binding free energy value (-8.76 kcal/mol) and interacts with important residues on the receptor forming four hydrogen bonds, namely the carbonyl group of SO2 with residues Trp111 and His110, and the carbonyl group of the amide with residues His110 and Tyr48, as well as 3 hydrophobic bonds, namely a pyrazole ring with residues Leu300, Trp219 and a furan ring with Phe122. ADMET properties of the compounds are also predicted. This information provides an opportunity for a 5C compound as an aldose reductase inhibitor agent to develop drug candidates with better and safer activities.

Synthesis, in vitro and in silico studies of pyrazole analogs as SARS-CoV-2 inhibitors

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a global pandemic disaster and a reason for millions of death worldwide. Developing a targeted therapy is highly beneficial to overcome the virulent disease. A series of pyrazole analogs were synthesized and screened against 3CLpro of SARS-CoV-2. Among thirty nine synthesized analogs, ten compounds displayed anti-SARS activity at 22 to 39 µM level. Also, the initial hits were subjected to docking studies to understand the binding mode and that insight studies may be helpful in further drug development of 3CLpro inhibitor of SARS-CoV-2.

Discovery of N-(1,4-Benzoxazin-3-one) urea analogs as Mode-Selective TRPV1 antagonists

A series of 1,4-benzoxazin-3-one analogs were investigated to discover mode-selective TRPV1 antagonists, since such antagonists are predicted to minimize target-based adverse effects. Using the high-affinity antagonist 2 as the lead structure, the structure activity relationship was studied by modifying the A-region through incorporation of a polar side chain on the benzoxazine and then by changing the C-region with a variety of substituted pyridine, pyrazole and thiazole moieties. The t-butyl pyrazole and thiazole C-region analogs provided high potency as well as mode-selectivity. Among them, antagonist 36 displayed potent and capsaicin-selective antagonism with IC50 = 2.31 nM for blocking capsaicin activation and only 47.5 % inhibition at 3 µM concentration toward proton activation, indicating that more than a 1000-fold higher concentration of 36 was required to inhibit proton activation than was required to inhibit capsaicin activation. The molecular modeling study of 36 with our homology model indicated that two π-π interactions with the Tyr511 and Phe591 residues by the A- and C-region and hydrogen bonding with the Thr550 residue by the B-region were critical for maintaining balanced and stable binding. Systemic optimization of antagonist 2, which has high-affinity but full antagonism for activators of all modes, led to the mode-selective antagonist 36 which represents a promising step in the development of clinical TRPV1 antagonists minimizing side effects such as hyperthermia and impaired heat sensation.

Synthesis, kinase inhibition and anti-leukemic activities of diversely substituted indolopyrazolocarbazoles

Pyrazole analogues of the staurosporine aglycone K252c, in which the lactam ring was replaced by a pyrazole moiety, were synthesized. In this series, one or the other nitrogen atoms of the indolocarbazole scaffold was substituted by aminoalkyl chains, aiming at improving protein kinase inhibition as well as cellular potency toward acute myeloid leukemia (AML) cell lines. Compound 19a, substituted at the N12-position by a 3-(methylamino)propyl group, showed high cellular activity in the low micromolar range toward three AML cell lines (MOLM-13, OCI-AML3 and MV4-11) with selectivity over non-cancerous cells (NRK, H9c2). 19a is also a highly potent inhibitor of the three Pim kinase isoforms, Pim-3 being the most inhibited with an IC50 value in the nanomolar range. A selectivity screening toward a panel of 50 protein kinases showed that 19a also potently inhibited PRK2 and to a lower extent AMPK, MARK3, GSK3β and JAK3. Our results enhance the understanding of the structural characteristics of indolopyrazolocarbazoles essential for potent protein kinase inhibition with therapeutic potential against AML.

An Efficient Synthesis of Curcumin Pyrazole Analogues and their Biological Activities

An Efficient Synthesis of Curcumin Pyrazole Analogues and their Biological Activities

Pharmacophore-based synthesis of pyrazole analogues as artificial antibiotics targeting Salmonella Typhi

The pharmacological potential of the pyrazole moiety is demonstrated by their presence in a wide range of therapeutic agents spanning various categories. Notable examples include: Celecoxib: A potent anti-inflammatory drug, 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB): An antipsychotic medication, Rimonabant: An anti-obesity drug, Difenamizole: An analgesic, Betazole: An H2-receptor agonist, Fezolamide: An antidepressant agent. These examples underscore the versatility and efficacy of the pyrazole nucleus in the development of pharmacologically active compounds across different therapeutic domains [1–12]. In our study, we computationally designed 23 different derivatives of pyrazole compounds and analysed their Pharmacokinetics (ADMET) properties in the QikProp module on Schrodinger's Maestro platform. Among them, high throughput optimised and promising analogues of 11 pyrazole compounds were synthesised and analysed by NMR and LCMS for structural configuration. The synthesised compounds were initially analysed for cytotoxicity by MTT assay and found to have lower toxicity profiling in 7 pyrazole derivatives. Further, the compounds were investigated for their antibacterial activity against Salmonella Typhi by broth dilution and disk diffusion methods, where four compounds (P4, P14, P19, and P20) exhibit a potential growth inhibitory activity as compared with standard antibiotics which commercially used for S. Typhi infection. Further, to explore the mode of action on the growth suppression of S. Typhi was investigated by performing molecular docking with outer membrane protein (cell wall inhibition) and DNA-dependant RNA polymerase (transcriptional arrest) of S. Typhi, wherein all four tested probes exhibited the binding interaction localised at the active domains of the foresaid target protein. The P14 compound exhibits the maximum score of least binding energy at -8.174 kcal/mol against OMP C, whereas the P4 remains at -5.575 kcal/mol against the DNA-dependent RNA polymerase. This observation is clearly evident in the antagonistic effects of the synthesised derivatives on the growth of S. Typhi.

A novel class of pyrazole analogues as aurora kinase A inhibitor: design, synthesis, and anticancer evaluation

Pyrazole, as a small molecule, was discovered for higher cytotoxicity and affinity towards Aurora-A kinase. Based on these facts, a novel pyrazole substituted at the 4th position was designed, synthesized, and evaluated against MCF-7, MDA-MB-23, and Vero (non-cancerous kidney cell) cell lines. Compounds5hand5eexhibited greater cytotoxicity in the series against MCF-7 and MDA-MB-231, with GI50 values of 0.12 µM and 0.63 µM, respectively, as compared to Imatinib (GI50 values of 16.08 µM and 10.36 µM). All of the compounds displayed selective cytotoxicity against cancer cells but not on normal Vero cells, supporting the design strategy to be a selective anticancer agent. Furthermore, compounds 5h and 5e inhibited Aurora-A kinase with IC50 values of 0.78 µM (4.70-fold) and 1.12 µM (2.84-fold), respectively, as compared to alisertib (IC50 = 3.36 µM). In addition, compound 5h significantly arrested the cell cycle at G2/M (34.89 %, 5.56-fold) and the apoptotic phase (25.04 %, 11.81-fold) compared to the control. It also triggered an increase in early (7.43 %) and late (14.89 %) phase apoptosis compared to vehicle (0.235 and 0.36 %, respectively), causing 37.89-fold higher total apoptosis in the annexin-V assay. These data imply that Aurora-A kinase inhibition may be linked to apoptosis induction and cell cycle arrest. Furthermore, their higher docking score in the study confirmed evidence of Aurora-kinase suppression. It was observed that fluorine and imidazole increased the H-bond and lipophilic interactions with the binding residue. Also, the substitution of electron-rich and lipophilic groups increased hydrophobic interactions. Moreover, the three-atom linkage (CH2NHCH2) expanded compound 5h to fill the cavity. Based on current findings, it is concluded that compounds 5h and 5e with strong Aurora-A kinase suppression may be promising anticancer agents.

Design, Synthesis and Antifungal Activities of Novel Pyrazole Analogues Containing the Aryl Trifluoromethoxy Group.

On the basis of the three-component synthetic methodology developed by us, a total of twenty-six pyrazole compounds bearing aryl OCF3 were designed and synthesized. Their chemical structures were characterized by 1H and 13C nuclear magnetic resonance and high-resolution mass spectrometry. These compounds were evaluated systematically for antifungal activities in vitro against six plant pathogenic fungi by the mycelium growth rate method. Most of the compounds showed some activity against each of the fungi at 100 μg/mL. Compounds 1t and 1v exhibited higher activity against all the tested fungi, and 1v displayed the highest activity against F. graminearum with an EC50 value of 0.0530 μM, which was comparable with commercial pyraclostrobin. Structure-activity relationship analysis showed that, with respect to the R1 substituent, the straight chain or cycloalkyl ring moiety was a key structural moiety for the activity, and the R2 substituent on the pyrazole ring could have significant effects on the activity. Simple and readily available pyrazoles with potent antifungal activity were obtained, which are ready for further elaboration to serve as a pharmacophore in new potential antifungal agents.

Synthesis, Molecular Docking and Characterization of Pyrazole N-Mannich Base Derivatives as Antimicrobial Agents

In this work we aimed to design synthesis and evaluate the N-Mannich bases of pyrazole. A novel series of N-Mannich bases of pyrazole analogues were designed and synthesized with an effort to overcome the increasing antibiotic resistance. Tyrosyl-tRNA synthetase (TyrRS) comprises an N-terminal domain, which has the fold of the class I aminoacyl-tRNA synthetases. Computational Autodock 4.2 tools will be employed in this study for docking of pyrazole ligand molecules against Tyrosyl-tRNA synthetase (TyrRS) of Escherichia coli (PDB code: 1x8x) and Staphylococcus aureus (PDB code: 1jil.pdb). Molinspiration server was used for lead optimization. The ligand molecules were subjected to molecular docking studies with enzyme Tyrosyl-tRNA synthetase. The molecular docking studies are supported to compare in-vitro antibacterial activity by the use of binding energy of the docked ligand molecules. The newly synthesized compounds were characterized by UV, IR and various physico-chemical methods. Further, the antibacterial activity of N-Mannich bases of pyrazole compounds were assessed with zone of inhibition by agar well diffusion method using gram negative bacterial strain Escherichia coli and gram-positive strain staphylococcus aureus. These same compounds were subjected to find the antifungal activity against Aspergillus fumigates and Aspergillus Niger.

Pharmacoinformatics-based strategy in designing and profiling of some Pyrazole analogues as novel hepatitis C virus inhibitors with pharmacokinetic analysis

ABSTRACT Hepatitis C virus (HCV) infection promotes death rates all over the world. Sofosbuvir is a standard drug for the cure of HCV but unfortunately, it receives a lot of attention for its pricing problems. As a result, it is crucial to consider alternative HCV treatments that are both cost-effective and free of side effects. We report how a pharmacoinformatics-based technique was used to generate and profile certain Pyrazole analogues as novel hepatitis C virus inhibitors by exploring the PubChem drug repository for the lead molecule with further optimization. The proposed molecules all interact by filling the protein target’s binding domain to inhibit the receptor. With binding energy of −35.72 kcal/mol, compound 17e was found as a highly potent NS5B inhibitor, exceeding Sofosbuvir, the FDA-approved NS5B inhibitor with a binding energy of −30.34 kcal/mol. Additionally, the ADMET assessment of the selected molecules (17e) shows outstanding quality with a drug score of 0.74 when especially in comparison to Sofosbuvir, which has a drug score of 0.31. Future studies should therefore focus on the molecular dynamics, synthesis, in vivo testing, and in vitro evaluation of these substances to validate our hypothesis.

Amino acid and Dicyclohexylurea Linked Pyrazole Analogues: Synthesis, In Silico and In Vitro Studies

AbstractPancreatic lipase (PL) inhibitors have received considerable attention by several researchers because of its ability to hydrolyse the triglycerides in the small intestine. This study reports the (i) synthesize of new pyrazole derivatives binding amino acid and Dicyclohexylurea (DCU), (ii) their pharmaceutical potentials‐ via enzyme inhibitory activity towards PL and antioxidant activities (using complementary antioxidant methods including FCR, FRAP and ORAC), (iii) the possible interactions between pyrazole compounds and PL enzyme through in silico studies, and the pharmacokinetic properties of the tetra‐substituted pyrazole analogues by PreADMET. Enzyme activities with IC50 values of the pyrazole analogues were found to be in a high range of 6.6±0.4 μM to 13.5±0.2 μM. However, antioxidant activities of the pyrazole analogues exhibited low binding affinities against FCR, FRAP, and ORAC. The pyrazole analogues with docking scores were in the range of −7.3 to −15.2 and their SAR analysis were demonstrated to highlight the importance of amino acid and DCU linked scaffolds. Two web tools were utilized for the purpose of predicting ADMET parameters of drugs and drug‐like pyrazole analogues. These results suggested that the amino acid and DCU linked pyrazole analogues have potential as PL inhibitors.

Design, synthesis, X-ray crystal structures, anticancer, DNA binding, and molecular modelling studies of pyrazole-pyrazoline hybrid derivatives.

We have designed and synthesized three pyrazole analogs (4, 5a, 5b), pyrazole-based chalcones (6a-6d) and (8a-8h), and N-formyl/acetyl 1,3,5-trisubstituted pyrazoline analogs (7a-7d), (9a-9d). FT-IR, 1H, 13C NMR, and mass spectrometry techniques were used to describe the structures of all the synthesized analogs. The single crystal X-ray method was used to identify the molecular structure of derivatives 4 and 5a. All synthesized analogs were screened by MTT assay on two cancer cell lines, the human lung cancer cell line (A549) and cervical cancer cell line (HeLa). Among all compounds, analog 9d demonstrates significant anticancer activity against HeLa (IC50 = 23.6 μM) and A549 (IC50 = 37.59 μM). The non-interactive interaction of active compound (9d) with Calf thymus DNA (Ct-DNA) has been investigated through various methods, such as UV-vis absorption, emission, cyclic voltammetry and circular dichroism. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical has been used to measure the antioxidant capacity of the pyrazoline derivative (9d). The outcomes showed that active analog has significant antioxidant activity. In addition, MD simulation of the EGFR tyrosine kinase protein-ligand complex was performed at a time scale of 100 ns. The MMGBSA data of ligand-protein complex are showed stable interactions up to 100 ns.

Tetra-substituted pyrazole analogues: synthesis, molecular docking, ADMET prediction, antioxidant and pancreatic lipase inhibitory activities

Tetra-substituted pyrazole analogues: synthesis, molecular docking, ADMET prediction, antioxidant and pancreatic lipase inhibitory activities

Design and synthesis of novel substituted pyrazole as small molecule inhibitor of cytochrome P450 CYP121A1

Discovering new drugs with novel targets is vital for the success of treatment of tuberculosis as antibiotic resistance is increasing among the TB population. Mycobacterium tuberculosis cytochrome P450 CYP121A1 is a promising drug target for the treatment of tuberculosis owing to its essential role in mycobacterium growth. Using a rational approach, that includes molecular docking studies of some substituted pyrazole derivatives a series of pyrazole analogue were designed and pass through computational studies. Compound with good docking score and ADME profile were synthesized using two step reaction and biologically evaluated for their inhibitory activity towards M. tuberculosis. All compounds were analyzed by IR, LCMS, 1H NMR and 13C NMR. Among them 3 compounds shows significant activity having MIC (6.25 µg/ml).

A Molecular Insight into Pyrazole Congeners as Antimicrobial, Anticancer, and Antimalarial Agents.

Pyrazole is a bioactive heterocyclic congener with numerous biological and pharmacological functionalities. Due to their multiple prospective applications, developing innovative and novel pyrazoles and analogs, revealing revolutionary methods for synthesizing this nucleus, investigating diverse potencies of that heterocycle, and exploring possible pyrazole applications are becoming increasingly relevant. Pyrazole scaffolds have been proven successful as antimicrobial, anticancer, and antimalarial therapeutics against multiple targets like DNA gyrase, topoisomerase IV, Hsp90, and several kinase enzymes. For this variability in the biotic zone, their moiety has gained the attention of many scientists interested in researching chemical and pharmacological profiles. The review covers pyrazole scaffolds with a variety of biological functions and attempts to connect the structure-activity relationship. Multiple pyrazole analogs have been produced as lead compounds, and their activities have been evaluated. The combination of pyrazole with other pharmacophores in a molecule might lead to novel potent therapeutic medicines, which could aid in the development of potent lead compounds.

Design, synthesis and evaluation of novel Se-alkylated pyrazoles and their cyclized analogs as potential anticancer agents

A simple multicomponent reaction (MCR) was utilized to synthesize a series of 5-alkylated selanyl-1H-pyrazole derivatives 3a-d, 6a-d, and their 4-amino-5-substituted selenolo[2,3-c]pyrazole analogs (4a-d). The methodology is based on the substitution of selenium for the chlorine atom in the chloro pyrazole carbonitrile compound 1via reduction with sodium borohydride in a nitrogen atmosphere, followed by in-situ substitution reactions with various α-halo alkylating agents in the presence of a basic catalyst. The structures of the compounds were confirmed using elemental and spectroscopic techniques (FT-IR, 1H, 13C NMR, and mass spectrometry). The compounds were screened for their anticancer activity which showed promising results and compounds 4c and 6d exhibited the highest cytotoxicity against the HepG2 cell line with pIC50 values of 4.30 and 4.49 respectively, without showing any off-target toxicity. These molecules also, displayed good ADMET features, passed Lipinski's filters, showed good drug-likeness properties, and were predicted to be effective dual EGFR and VEGFR-2 inhibitors, causing downregulation of S100A4 and MMP-9 genes. Together, these results make these molecules as important lead molecules that could be studied further for their anticancer properties.

Design, synthesis, and biological activity of novel spiro-pyrazolo[1,5-a]quinazolines derivatives as potential insecticides.

Arylpyrazole insecticides display broad-spectrum insecticidal activity against insect pests. However, the high toxicity toward honeybees associated with fipronil prohibits its agronomic utility. To explore reducing the toxicity of aryl pyrazole analogs to bees, a series of new spiro-pyrazolo[1,5-a]quinazoline derivatives were designed and synthesized. Bioassay results showed that these compounds exhibited good insecticidal activity. In particular, the insecticidal activity of compound 5f against Plutella xylostella larvae (median lethal contentration, LC50 =1.43 mg L-1 ) was equivalent to that of fipronil. Moreover, some compounds also showed good insecticidal activity against Solenopsis invicta. Importantly, the bee toxicity study confirmed that compound 5f had much lower acute oral toxicity, with a median lethal dose (LD50 ) = 1.15 μg bee-1 that was three to four orders of magnitude greater than that of fipronil (0.0012 μg bee-1 ). Electrophysiological studies were conducted using honeybee γ-aminobutyric acid receptor heterologously expressed in Xenopus oocytes to explain the reduced bee toxicity of compound 5f. The inhibitory effect of compound 5f (16.29 μmol L-1 ) was determined to be approximately 700-fold lower than that of fipronil (0.023 μmol L-1 ). These spiro-pyrazolo[1,5-a]quinazoline derivatives could be potential candidates and lead structures for the discovery of novel insecticides with low bee toxicity. © 2022 Society of Chemical Industry.

Discovery of a Series of 5-Amide-1H-pyrazole-3-carboxyl Derivatives as Potent P2Y14R Antagonists with Anti-Inflammatory Characters.

UDPG/P2Y14R signaling pathway has been considered as a potential therapeutic target for innate immune system diseases. Based on the scaffold hopping strategy, a series of pyrazole analogues were designed and synthesized as novel P2Y14R antagonists with improved physicochemical properties, together with potential anti-inflammatory activities. Additionally, we designed and synthesized a fluorescent probe based on highly selective and potent PPTN to study the affinity of synthesized compounds. The optimized compound 16 (1-(4-fluorobenzyl)-5-(4-methylbenzamido)-1H-pyrazole-3-carboxylic acid, P2Y14R IC50 = 1.93 nM) showed strong binding ability to P2Y14R, high selectivity, notably improved solubility, and more favorable pharmacokinetic profiles. Moreover, compound 16 possessed extremely low cytotoxicity and anti-inflammatory effect in vitro. In an acute peritonitis model, compound 16 could effectively reduce the levels of inflammatory factor IL-6, IL-1β, and TNF-α of mice induced by LPS. Compound 16, with potent in vitro and in vivo efficacy and favorable druggability, can be a promising candidate for further research.

Synthesis, biological evaluation and molecular docking of new triphenylamine-linked pyridine, thiazole and pyrazole analogues as anticancer agents

A new series of pyridine, thiazole, and pyrazole analogues were synthesized. The pyridone analogues 4a-e were synthesized by treating N-aryl-2-cyano-3-(4-(diphenylamino)phenyl)acrylamides 3a-e with malononitrile. Many 4-arylidene-thiazolidin-5-one analogues 6a-d were obtained by Knoevenagel reactions of 4-(diphenylamino)benzaldehyde (1) with their corresponding thiazolidin-5-one derivatives 5a-d. The structural elucidation of the products was proven by the collections of spectroscopic methods such as IR, 1H NMR, 13C NMR, and MS data. Their anti-cancer activity was examined against two cell lines, MDA-MB-231 (mammary carcinomas) and A-549 (lung cancer). Compared with cisplatin as a reference standard drug, 6-amino-4-(4-(diphenylamino)phenyl)-2-oxo-1-(p-tolyl)-1,2-dihydropyridine-3,5-dicarbonitrile (4b) and 6-amino-4-(4-(diphenylamino)phenyl)-1-(4-nitrophenyl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile (4e) exhibited better efficiency against the A-549 cell line, with IC50 = 0.00803 and 0.0095 μM, respectively. Also, these compounds 4b and 4e showed the most potency among the examined compounds against MDA-MB-231 with IC50 = 0.0103 and 0.0147 μM, respectively. The newly synthesized compounds were docked inside the active sites of the selected proteins and were found to demonstrate proper binding. 2-Cyano-2-(4,4-(diphenylamino)benzylidene)-5-oxo-3-phenylthiazolidin-2-ylidene)-N-(p-tolyl)acetamide (6c) offered the highest binding affinity (− 8.1868 kcal/mol) when docked into (PDB ID:2ITO), in addition to 2-cyano-N-(4-(diethylamino)phenyl)-2-(4-(4-(diphenylamino)benzylidene)-5-oxo-3-phenylthiazolidin-2-ylidene)acetamide (6a) gave the highest energy score (− 9.3507 kcal/mol) with (PDB ID:2A4L).