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Pyrazoline derivatives exhibit a variety of biological activities, such as antifungal, antiviral, and antibacterial. Biological effects depend on the type of substituents and their position in the ring. [1] The aim of this study was to evaluate the inhibitory effects of fluorinated pyrazole aldehydes against plant pathogenic fungi (Fusarium oxysporum f. sp. lycopersici, Fusarium culmorum, Macrophomina phaseolina and Sclerotinia sclerotiourum). The compounds demonstrated moderate activity against phytopathogenic fungi. The highest efficiency has shown 2-chlorophenyl derivative (H9) against F. culmorum (46.75%). In order to determine the binding affinity and interactions of the most active compounds with three enzymes responsible for the fungal growth and the three plant cell wall-degrading enzymes, molecular docking was performed. In order to determine the possible mechanism of action of derivatives against pathogenic fungi, molecular docking study has been performed on three enzymes responsible for the fungal growth: demethylase (sterol 14α-demethylase (CYP51), PDB: 5EAH) ; chitinase (PDB: 4TXE) ; transferase (N-myristoyltransferase, PDB: 2P6G) ; and the three plant cell wall-degrading enzymes: endoglucanase I (PDB: 2OVW) ; proteinase K (PDB: 2PWB) ; pectinase (endopolygalacturonase, PDB: 1CZF). The future derivatives should be designed to be more effective against pathogenic fungi without negative effects on beneficial organisms, environment pollution, and human health

Rhodanines have been reported to possess antibacterial, antiviral, antimalarial, antifungal, and antitumor activity. A series of novels rhodanine derivatives were assayed for their cytotoxic activity against a panel of human cancer cell lines. Quantitative structure-activity relationship (QSAR) analysis was performed on the anticancer activity against cutaneous T lymphocyte (cell line Hut-78) since 98 % of compounds have achieved the concentration achieving 50% cell growth inhibition (GI50) 100 μM. QSAR study of the anticancer activity against HUT-78 achieved the model that satisfies the fitting and internal cross-validation criteria (N = 28 ; R2 = 0.75 ; Q2 LOO = 0.64): logGI50 = 2.51 – 3.46 MATS2e – 1.05 MATs7e – 0.15 RDF060p Descriptors included in the model revealed the importance of the presence of atoms with higher polarizability in the outer region of molecules. Molecules that possess 3- methoxy group (ALR9) and 3-bromine (ALR16) at the benzene ring proved to be potential drug candidates against human T cell lymphoma since inhibited 50% growth of cells Hut-78 at the very low concentration (3 and 7.5 μmol dm-3, respectively). Also, the presence of electronegative atoms at the topological distances 2 and 7, such as hydroxyl and ethoxy groups as substituents of the benzylidene group decreases the activity. A molecular docking study confirmed the findings of the QSAR study regarding the structural features related to the inhibition of nonreceptor proteintyrosine kinase (c-Src) (PDB ID: G6H) and indicated importance of the oxygen atoms from phenoxy and rhodanine groups, and rhodanine sulphur atoms as hydrogen bond acceptors in key interactions with binding site residues, as well as benzene rings in generations of van der Waals interactions. Our study suggests that rhodanine derivatives could be developed as novel tyrosine kinase inhibitors in the treatment of leukemia.

Phytopathogenic fungi are one of the leading causes of plant diseases that reduce crop quality and cause huge yield losses. The control of fungal plant diseases is important for reducing or preventing these losses. The excessive use of available fungicides over a long period of time has increased the fungal resistance and become a major ecological issue, giving the incentive to find new antifungal agents. Quinazolinone is a common heterocyclic nitrogen scaffold, widely present in natural products. Its derivatives exert a variety of biological activities, such as antitumor, antiviral, antibacterial and antifungal. The aim of this study was to examine a potential antifungal activity of several structurally different, recently synthesized new quinazolinone derivatives using a computational approach. A molecular docking analysis has been performed on two fungal chitinases, type A (PDB ID: 2XUC) and B (PDB ID: 2IUZ), involved in chitin decomposition, cell wall degradation and remodeling. Molecular docking has shown that all tested compounds bind near the enzyme active sites. The most promissing compounds were N2, N6- bis(2-methyl-4- oxoquinazolin-3(4H)-yl)pyridine-2, 6-dicarboxamide for chitinase A, and 3-(4- methoxyphenyl)-2- methyl-6-nitroquinazolin-4(3H)- one for chitinase B.

Human dipeptidyl peptidase III (hDPP III) is a zinc‐hydrolase that cleaves dipeptides sequentially from the N‐ terminal of different bioactive peptides. Although the physiological role of hDPP III is not yet fully elucidated, its involvement in pathophysiological processes such as mammalian pain modulation and blood pressure regulation emphasizes the need to find new hDPP III inhibitors. Coumarins exhibit a variety of biological activities, and Schiff bases bearing coumarin moiety in conjunction with the imino group (-C=N-) form significant compounds in medicinal and pharmaceutical chemistry. To find new potential inhibitors of hDPP III, in this research we selected 6 coumarinyl Schiff bases to investigate their interactions with hDPP III, combining experimental and computational approaches. hDPP III activity was determined using the spectrophotometric assay, while molecular docking was performed by AutoDock Vina software to obtain information regarding the possible interactions of the strongest inhibitor and hDPP III binding site. The experimental results showed that all analyzed compounds have an inhibitory effect against hDPP III activity at the physiological concentration i.e., 100 μM. The strongest inhibition (87.9 %) has been obtained with compound 5. Docking predicts that 5 interacts with amino acid residues of hDPP III mostly in the region of inter-domain cleft by forming hydrogen bonds with Ile386, His568 and Arg572, π – interactions with Phe109, Pro387 and Ala388, and numerous van der Waals interactions. Most of these residues are found to be constituents of the hDPP III substrate binding subsites S1, S1’, S2, S2’ and S3’. The results of this study provide an insight into the coumarinyl Schiff bases inhibitory activity and interactions toward hDPP III.

Acetylcholinesterase (AChE) is an enzyme responsible for the metabolism of acetylcholine (ACh), the neurotransmitter controlling motor activities in nematodes. Inhibition of AChE results in accumulation of ACh at neuromuscular junctions and leads to paralysis, which makes AChE a good target enzyme for the control of parasitic nematodes. AChE inhibitors used to control parasitic nematodes are mainly organophosphates and carbamates, however, due to their toxicity, they have been withdrawn or have restricted usage. Halogenated pyrazoline derivatives exhibit various biological activities, among them antibacterial, antifungal, and antimicrobial. A series of fluorinated pyrazolines was chosen for the investigation of possible AChE inhibition, using Ellman’s protocol modified for microplate reader. All tested compounds exhibited moderate to good inhibitory effect against AChE at 50 μM concentration, with compound 9 (Fig. 1) having the highest inhibition of 79.5 %. A molecular docking study was performed to gain insight into the binding interaction of compound 9 with AChE (PDB: 2c5g). Results show that compound 9 interacts with amino acid residues located in the peripheral active site of AChE, blocking the narrow passage to the catalytic site. The effect of fluorinated pyrazolines was also tested on two entomopathogenic nematodes, Heterorhabditis bacteriophora, and Steinernema feltiae. Entomopathogenic nematodes are beneficial nematodes used in insect pest management programs because of their resilience to pesticide exposure. Since these nematodes mostly have been unaffected by tested compounds, it indicates their potential use as plant protection agents.

Human dipeptidyl peptidase III (hDPP III) is a zinc‐hydrolase that cleaves dipeptides from the N‐ terminal of different bioactive peptides. Quinazolinones belong to a diverse class of nitrogen-containing heterocyclic compounds, derivatives of which exhibit a wide range of biological activities. In this research, we selected 10 previously synthesized [1] structuraly different quinazolinone derivatives (QDs) to investigate their potential to inactivate hDPP III activity combining in vitro and in silico approach. The experimental results showed that all analyzed QDs (at the physiological concentration i.e., 100 μM) have inhibitory effect against hDPP III activity. The strongest inhibition (% inh. = 81.9) has been obtained with compound QD8. Molecular docking revealed that hDPP III interacts mostly by hydrogen bonds and hydrophobic interactions with QD8. Among important intermolecular interactions are those with amino acid residues F443, Q446, V447, H568 and R572 that are constituents of hDPP III substrate binding subsites S1, S1’, S2’, and S3’.

Phosphodiesterase type 5 (PDE5) is a cyclic guanosine monophosphate (cGMP)-specific enzyme and mostly expressed in smooth muscle tissue of corpus cavernosum, heart, lung, platelets, prostate, urethra, bladder, liver, brain, and stomach. Inhibitors of PDE5, prevent the hydrolysis of cGMP and become effective treatment to diseases associated with low cGMP level, such as pulmonary arterial hypertension. [1] It has been well-documented that pyrazole- containing compounds diverse chemotherapeutic potentials, such as antileukemic and antiproliferative agents. Beside, halogenated organic compounds has been widely use as many drug candidates. [2] Recently, we have synthesized a novel series of halogenated pyrazolines. Molecular docking study was performed to explain in silico the binding interaction with the PDE5 (PDB: 4oew). Molecular docking has confirmed that compound 5-(2, 6-dimethoxyphenyl)-3-(4-fluorophenyl)-4, 5-dihydro-1H-pyrazole-1-carbaldehyde has lowest total energy binding (-105, 69 kcal/mol). The binding interactions of the most active compound have shown strong hydrogen bonding and van der Waals interactions with the target protein.