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Coumarins and triazoles are two interesting groups of heterocyclic compounds, both exhibiting a wide range of biological activities. The joining of these two scaffolds into a hybrid compound with the improved activities has already been reported. [1] In this research, 11 new hybrid compounds were synthesized, utilizing a deep eutectic solvent as an environmentally sustainable method of organic synthesis. Compounds were obtained in good yields through a one-step reaction of coumarinyl hydrazides and various substituted isothiocyanates, without the use of catalysts. [2] Since many commercially available fungicides are based on triazole derivatives, antifungal activity of 1, 2, 4-triazolyl coumarins was evaluated in vitro on two pathogenic fungi, Fusarium oxysporum and Fusarium culmorum. The tested compounds moderately inhibited the mycelial growth of F. oxysporum (35.0-57.5%), but were mostly ineffective against F. culmorum. Compound 1b, as the most potent growth inhibitor, was further analyzed computationally. A molecular docking analysis was performed to evaluate the binding mode of compound 1b with sterol 14 α-demethylase, the target enzyme of triazole based fungicides

The substantial increase in pest’s resistance to commonly used pesticides as well as the concern of growing environmental pollution have been the biggest challenges agricultural industry had to face in recent years. Large efforts have been made to produce a variety of novel and environmentally sustainable compounds to be used as an alternative to commercially available pesticides. [1] A set of 36 newly synthesized triazole derivatives have been assayed as potential acetylcholinesterase inhibitors by utilizing the Ellman’s protocol. [2] The highest inhibition percentages were obtained with compounds 7h (68.32%), KM35 (49.77%), KM16 (48.04%), KM18 (47.82%), and KM19 (39.89%). In vivo study was performed on two species of nematodes ; Heterorhabditis bacteriophora and Steinernema feltiae. The nematodes were exposed to aforementioned compounds in the period of 72 h. The highest mortality rate of Heterorhabditis bacteriophora species was observed with the compound KM16 with the value of 75.0% after 48 h of incubation, while he highest mortality rate of Steinernema feltiae was observed with the compound KM18 with the value of 50.0% after 48 and 72 h of incubation. The inhibition percentages do not seem to correlate with the in vivo results, as the compound 7h had one of the lowest mortality rates within the tested group of compounds among the both nematode species.

Novel derivates of benzothiazoles and benzimidazoles have been evaluated on T-cell lymphoma (HuT78), as well as on normal Madin-Darby canine kidney cells (MDCK-1). Cytotoxic effects of 77 benzothiazoles and benzimidazoles against non-tumour MDCK-1 cells were ranked by activities, and 17 compounds were chosen for the test set. The best QSAR model expressed by multiple linear regression equation was generated by five molecular descriptors calculated by DRAGON program: SIC1, GATS4p, BEHv6, BELp1, and R7m. Williams plot of the applicability domain, detected one molecule as a border outlier and no molecule out of the warning leverage. After removing outlier, the new model has the model achieved better statistical performance of internal and external validation: R2train = 0.74 ; F = 30.76 ; ΔK = 0.08 ; CCCtr = 0.85 ; Q2loo = 0.68 ; CCCcv = 0.81 ; R2Yscr = 0.09 ; Q2Yscr = -0.13 ; R2ext = 0.83 ; CCCext = 0.85 ; Δr2m = 0.25. Molecules without atoms with higher atomic mass as substituents (Cl, F) and more equal neighbor atoms have higher activity. QSAR study for antiproliferative activity on T-cell lymphoma (HuT78) cell was performed on a total of 59 molecules (47 training, 12 test set). The best-obtained model includes three descriptors: MATS8v, Mor09p, Mor30m, and E2u. After exclusion of three outliers from data set, relived by Williams plot (Figure 1) resulted on the predictive model: R2train = 0.87 ; F = 66.48 ; ΔK = 0.12 ; CCCtr = 0.93 ; Q2loo = 0.83 ; CCCcv = 0.91 ; R2Yscr = 0.09 ; Q2Yscr = -0.15 ; R2ext = 0.87 ; CCCext = 0.85 ; Δr2m = 0.13. An increasing number of atomic van der Waals volumes, such as in sulphur atom in benzothiazoles, as molecules without atoms, have higher atomic mass as substituents (Cl, F) enhancing antiproliferative activity on MDCK-1 cells.

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.

Molecular docking study was performed to identify new lead inhibitor of SARS-CoV-2 spike glycoprotein (S protein) from the set of 62 peptide derivatives and evaluate their interactions with the receptor. Peptide-type compounds are previously proven peptide-type SARS- CoV 3CL protease inhibitors. However, highest binding affinity towards S protein has compound 21 (E = -127.2 kcal/mol), which showed the very low inhibitory activity against SARS- CoV 3CL protease. Compound 21 is in conformation that tightly fits along only the subunit S1, making the interactions with RBD and SD2 residues. Formation of a cluster of H- atom acceptor (O and N atoms), allows stronger binding to S1 subdomain. Antiviral drug Remdesivir demonstrated low binding affinity toward the S protein. Compounds that interact with receptor binding domain of SARS-CoV-2 spike glycoprotein may be potential therapeutic targets for drug design against COVID-19.

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’.

Polimerni nanokompoziti kao što su sustavi polimer/kvantne točke u začetcima njihovog istraživanja, prvenstveno su sintetizirani kako bi se pokušala poboljšati svojstva pojedinih komponenti sustava. Ovaj rad daje pregled istraživanja koja se bave sintezom i testiranjem svojstava pojedinih sustava polimer/kvantne točke različitih izvedbi kao što su sustavi polimerni koloidi/kvantne točke, naizmjenični slojevi polimer/kvantne točke, te sustavi s kvantnim točkama u masi polimerima i tankim polimernim filmovima. Različite izvedbe sustava posljedično zahtijevaju različite načine sinteze, koje utječu na različita svojstva i područja primjene sustava polimer/kvantne točke. Pregledom brojnih publikacija koje opisuju istraživanja sustava polimer/kvantne točke, pokazano je kako je kontroliranom sintezom kvantnih točaka, odabirom povoljnog polimera, te jednostavnom pripravom sustava polimer/kvantne točke moguće poboljšati svojstva kvantnih točaka u područjima njihove primjene. At the inception of their research, polymer nanocomposites such as polymer/quantum dots systems were primarily synthesized in order to improve the properties of certain system components. This paper provides an overview of the researches involved in the synthesis and testing of the properties of individual polymer/quantum dots systems of various performances such as polymeric colloids/quantum dots systems, alternating layers of polymer/quantum dots systems, and systems of quantum dots in bulk polymers and thin polymer films. Different system performances therefore require different synthesis modes, which affect the different properties and application areas of the polymer/quantum dots systems. By reviewing numerous publications describing the research of the polymer/quantum dots systems, it has been shown that by using the controllable quantum dot synthesis, selecting the favorable polymer, and using the fairly simple synthesis methods of polymer/quantum dots systems, quantum dot properties can be improved in the areas of their applications.