Lysine-specific demethylase 1 (LSD1) is abnormally overexpressed in various tumour tissues of patients and has been an attractive anticancer target. In this work, a potent LSD1 inhibitor (compound 14) was designed and synthesised by the molecular hybridisation strategy. It displays the potent antiproliferative activity against HepG2, HEP3B, HUH6, and HUH7 cells with IC50 values of 0.93, 2.09, 1.43, and 4.37 μM, respectively. Furthermore, compound 14 is a selective and reversible LSD1 inhibitor with an IC50 value of 0.18 μM and increases the methylation levels of H3K4me1/2. Molecular docking studies showed that it formed hydrogen bonds, hydrophilic interactions and hydrophobic interactions with residues of LSD1. Anticancer mechanisms demonstrated that it suppresses migration and epithelial-mesenchymal transition process in HepG2 cells. Importantly, it exhibits potent anti-liver cancer effects in vivo without obvious toxic effects. These interesting findings suggested that compound 14, a novel LSD1 inhibitor, may be a promising therapeutic agent to treat liver cancer.

The goal of this work was to synthesize new compounds for anticancer evaluation as a trial to obtain new antitumor agents with higher activity and fewer side effects. Therefore, the precursor 2,2'-(1,4-phenylenebis (thiazole-4,2-diyl))bis (3-(dimethylamino)acrylonitrile) (4) was used to synthesize various azolopyrimidine derivatives connected to the thiazole moiety. Compounds 5-11, including pyrazolopyrimidine, triazolopyrimidine, and others, were produced by reacting enaminonitrile 4 with different N-nucleophiles. Additionally, compounds 12-15, such as isoxazole and pyrimidinethione derivatives, were obtained by reacting compound 4 with guanidine, hydrazine hydrate, hydroxylamine hydrochloride, and thiourea. Enaminonitrile 4 was also treated with barbituric acid, isoxazolone, and pyrazolone to yield pyranopyrimidine derivatives 18-20. Moreover, enaminonitrile 4 reacts with C-nucleophiles namely ''acetylacetone, dimedone, 2-cyanomethylbenzothiazole, and 2-cyanomethylbenzimidazole'' to give pyrano derivatives 21, 22 and fused pyridone derivatives 23 and 24, respectively. The cytotoxic activity of 20 novel compounds against HSV-1, HIV-1, and various cancer cell lines was assessed, with compounds 5, 7, and 9 showing the strongest effects. Molecular docking studies further evaluated the binding affinity of these derivatives, with docking scores ranging from -7.8679 to -8.3013 kcal/mol. Several new azolopyrimidine derivatives linked to the thiazole moiety were effectively synthesized and assessed in the study, and they showed notable cytotoxic activity against HSV-1, HIV-1, and several cancer cell lines.

Natural products (NPs) are privileged structures interacting with biomacromolecular targets and exhibiting biological effects important for human health. In this review, we have presented NP-inspired strategic innovations that are promising for addressing preclinical and clinical challenges. An analysis of 'molecule-to-medicinal' properties for improvement of P3 and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles has been illustrated. The strategies include chemical evolution through knowledge of structure-medicinal properties, truncation of NPs to avoid molecular obesity, pseudo-NPs, selection of common structural features of NPs, medicinophore installation, scaffold hopping, and induced proximity. Molecule-to-medicinal property analysis can guide the development of 'nature-to-new' chemical therapeutics. Coupled with scientific advances and innovations in instrumentation, these strategies hold great potential for enhancing drug design and discovery.

Multidrug resistance (MDR) mechanisms in cancer cells are greatly influenced by glutathione transferase P1-1 (hGSTP1-1). The use of synthetic or natural compounds as hGSTP1-1 inhibitors is considered an effective approach to overcome MDR. Nine compounds consisting of coumarin-6-sulfonamide linked to chalcone derivatives were synthesized and evaluated for their ability to inhibit hGSTP1-1. Among the synthetic derivatives, compounds 5g, 5f, and 5a displayed the most potent inhibitory effect, with IC50 values of 12.2 ± 0.5 μΜ, 12.7 ± 0.7 and 16.3 ± 0.6, respectively. Kinetic inhibition analysis of the most potent molecule, 5g, showed that it behaves as a mixed-type inhibitor of the target enzyme. An in vitro cytotoxicity assessment of 5a, 5f, and 5g against the human prostate cancer cell lines DU-145 and PC3, as well as the breast cancer cell line MCF-7, demonstrated that compound 5g exhibited the most pronounced cytotoxic effect on all tested cell lines. Molecular docking studies were performed to predict the structural and molecular determinants of 5g, 5f, and 5a binding to hGSTP1-1. In agreement with the experimental data, the results revealed that 5g exhibited the lowest docking score among the three studied inhibitors as a consequence of shape complementarity, governed by van der Waals, hydrogen bonds and a π-π stacking interaction. These findings suggest that coumarin-chalcone hybrids offer new perspectives for the development of safe and efficient natural product-based sensitizers that can target hGSTP1-1 for anticancer purposes.

The escalating threat of drug-resistant microbes underscores the urgent need for novel antimicrobial agents. In response, considerable research effort has been directed towards developing innovative frameworks and strategies to address this challenge. Chalcones, known for their broad-spectrum biological activities, have emerged as promising candidates for combating drug resistance. In this study, a series of 2'-Hydroxychalcones (5a, 5b, 5c, and 5d) with varying electron withdrawing and donating groups were synthesized via Claisen Schmidt condensation. FT-IR, 1H NMR, and 13C NMR analyses were employed to confirm the structure of the synthesized compounds. Subsequent evaluation of the synthesized compounds revealed their potential as antibacterial and antibiofilm agents. Notably, compounds 5a and 5d exhibited potent antibacterial activity against multidrug-resistant (MDR) bacteria E. coli, P. aeruginosa, K. pneumoniae, and S. aureus, surpassing the reference drug Ciprofloxacin (30 μg/mL) and other synthesized compounds. Compound 5d showed a notable 19.5 mm zone of inhibition against K. pneumoniae. Furthermore, 5a (at a concentration of 30 μg) and 5d (at a concentration of 50 μg) exhibited statistically significant (P > 0.05) biofilm inhibition efficacy compared to Ciprofloxacin (30 μg/mL). The synthesized chalcones 5a-5d were also docked via PachDock molecular docking software for Glucosamine-6-phosphate (GlcN-6-P) synthase inhibition and showed that ligand 5a exhibited outstanding results with score 4238 and ACE value -160.89 kcal/mol, consistent with the observed antibacterial activity. These findings underscore the potential of chalcones, particularly 5a and 5d, as promising candidates for the development of new antimicrobial agents targeting drug-resistant microbes and biofilm formation.

Molecular hybridization represents a new approach in drug discovery in which specific chromophores are strategically combined to create novel drugs with enhanced therapeutic effects. This innovative strategy leverages the strengths of individual chromophores to address complex biological challenges, synergize beneficial properties, optimize pharmacokinetics, and overcome limitations associated with single-agent therapies. Coumarins are documented to possess several bioactivities and have therefore been targeted for combination with other active moieties to create molecular hybrids. This review summarizes recent (2013-2023) trends in the synthesis of coumarins, as well as coumarin-chalcone and coumarin-triazole molecular hybrids. To cover the wide aspects of this area, we have included differently substituted coumarins, chalcones, 1,2,3- and 1,2,4-triazoles in this review and considered the point of fusion/attachment with coumarin to show the diversity of these hybrids. The reported syntheses mainly relied on well-established chemistry without the need for strict reaction conditions and usually produced high yields. Additionally, we discussed the bioactivities of the reported compounds, including antioxidative, antimicrobial, anticancer, antidiabetic, and anti-cholinesterase activities and commented on their IC50 where possible. Promising bioactivity results have been obtained so far. It is noted that mechanistic studies are infrequently found in the published work, which was also mentioned in this review to give the reader a better understanding. This review aims to provide valuable information to enable further developments in this field.

In recent decades, the utilization of microwave energy has experienced an extraordinary surge, leading to the introduction of innovative and revolutionary applications across various fields of chemistry such as medicinal chemistry, materials science, organic synthesis and heterocyclic chemistry. Herein, we provide a comprehensive literature review on the microwave-assisted organic synthesis of selected heterocycles. We highlight the use of microwave irradiation as an effective method for constructing a diverse range of molecules with high yield and selectivity. We also emphasize the impact of microwave irradiation on the efficient synthesis of N- and O-containing heterocycles that possess bioactive properties, such as anti-cancer, anti-proliferative, and anti-tumor activities. Specific attention is given to the efficient synthesis of pyrazolopyrimidines-, coumarin-, quinoline-, and isatin-based scaffolds, which have been extensively studied for their potential in drug discovery. The article provides valuable insights into the recent synthetic protocols and trends for the development of new drugs using heterocyclic molecules.

Free radicals and oxidants may cause various damages both to the lifeworld and different products. A typical solution for the prophylaxis of oxidation-caused conditions is the usage of various antioxidants. Among them, various classes are found-polyphenols, conjugated polyalkenes, and some sulfur and nitrogen derivatives. Regarding the active site in the molecules, a widely discussed group of compounds are 1,3-dicarbonyl compounds. Among them are natural (e.g., curcumin and pulvinic acids) and synthetic (e.g., 4-hydroxy coumarins, substituted Meldrum's acids) compounds. Herein, information about various compounds containing the 1,3-dicarbonyl moiety is covered, and their antiradical and antioxidant activity, depending on the structure, is discussed.

We built the Curcumin Chalcone Derivatives Database (CCDD) to enable the effective virtual screening of highly potent curcumin and its analogs. The two-dimensional (2D) structures were drawn using the ChemBioOffice package and converted to 3D structures using Discovery Studio Visualizer V 2021 (DS). The database was built using different Python modules. For the 3D structures, different Python packages were used to obtain the data frame of compounds. This framework is also used to visualize the compounds. The webserver enables the users to screen the compounds according to Lipinski's rule of five. The structures can be downloaded in .sdf and .mol format. The data frame (df) can be downloaded in .csv format. Our webserver can help computational drug discovery researchers find new therapeutics and build new webservers. The CCDD is freely available at: https://srampogu-ccdd-ccdd-8uldk8.streamlit.app/.

Ubiquitously present in plant life, coumarins, as a class of phenolic compounds, have multiple applications-in everyday life, in organic synthesis, in medicine and many others. Coumarins are well known for their broad spectrum of physiological effects. The specific structure of the coumarin scaffold involves a conjugated system with excellent charge and electron transport properties. The antioxidant activity of natural coumarins has been a subject of intense study for at least two decades. Significant research into the antioxidant behavior of natural/semi-synthetic coumarins and their complexes has been carried out and published in scientific literature. The authors of this review have noted that, during the past five years, research efforts seem to have been focused on the synthesis and examination of synthetic coumarin derivatives with the aim to produce potential drugs with enhanced, modified or entirely novel effects. As many pathologies are associated with oxidative stress, coumarin-based compounds could be excellent candidates for novel medicinal molecules. The present review aims to inform the reader on some prominent results from investigations into the antioxidant properties of novel coumarin compounds over the past five years.

Herein, we report the experimental evaluation of the antimicrobial activity of seventeen new (Z)-methyl 3-(4-oxo-2-thioxothiazolidin-5-ylidene)methyl)-1H-indole-2-carboxylate derivatives. All tested compounds exhibited antibacterial activity against eight Gram-positive and Gram-negative bacteria. Their activity exceeded those of ampicillin as well as streptomycin by 10-50 fold. The most sensitive bacterium was En. Cloacae, while E. coli was the most resistant one, followed by M. flavus. The most active compound appeared to be compound 8 with MIC at 0.004-0.03 mg/mL and MBC at 0.008-0.06 mg/mL. The antifungal activity of tested compounds was good to excellent with MIC in the range of 0.004-0.06 mg/mL, with compound 15 being the most potent. T. viride was the most sensitive fungal, while A. fumigatus was the most resistant one. Docking studies revealed that the inhibition of E. coli MurB is probably responsible for their antibacterial activity, while 14a-lanosterol demethylase of CYP51Ca is involved in the mechanism of antifungal activity. Furthermore, drug-likeness and ADMET profile prediction were performed. Finally, the cytotoxicity studies were performed for the most active compounds using MTT assay against normal MRC5 cells.

Fungal deterioration is one of the major factors that significantly contribute to mummy cartonnage damage. Isolation and molecular identification of thirteen fungal species contributing to the deterioration of ancient Egyptian mummy cartonnage located in El-Lahun regions, Fayoum government, Egypt was performed. The most dominant deteriorated fungal species are Aspergillus flavus (25.70%), Aspergillus terreus (16.76%), followed by A. niger (13.97%). A newly synthesized series of tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline chalcone derivatives were synthesized and evaluated for their antifungal activities in vitro against the isolated deteriorated fungal species (Aspergillus flavus, A. niger, A. terreus, Athelia bombacina, Aureobasidium iranianum, Byssochlamys spectabilis, Cladosporium cladosporioides, C. ramotenellum, Penicillium crustosum, P. polonicum, Talaromyces atroroseus, T. minioluteus and T. purpureogenus). The most efficient chalcone derivatives are new chalcone derivative numbers 9 with minimum inhibitory concentration (MIC) ranging from 1 to 3 mg/mL followed by chalcone derivatives number 5 with MIC ranging from 1 to 4 mg/mL.

Chalcones are natural substances found in the metabolism of several botanical families. Their structure consists of 1,3-diphenyl-2-propen-1-one and they are characterized by having in their chains an α, β-unsaturated carbonyl system, two phenol rings and a three-carbon chain that unites them. In plants, Chalcones are mainly involved in the biosynthesis of flavonoids and isoflavonoids through the phenylalanine derivation. This group of substances has been shown to be a viable alternative for the investigation of its antibacterial potential, considering the numerous biological activities reported and the increase of the microbial resistance that concern global health agencies. Staphylococcus aureus is a bacterium that has stood out for its ability to adapt and develop resistance to a wide variety of drugs. This literature review aimed to highlight recent advances in the use of Chalcones and derivatives as antibacterial agents against S. aureus, focusing on research articles available on the Science Direct, Pub Med and Scopus data platforms in the period 2015-2021. It was constructed informative tables that provided an overview of which types of Chalcones are being studied more (Natural or Synthetic); its chemical name and main Synthesis Methodology. From the analysis of the data, it was observed that the compounds based on Chalcones have great potential in medicinal chemistry as antibacterial agents and that the molecular skeletons of these compounds as well as their derivatives can be easily obtained through substitutions in the A and B rings of Chalcones, in order to obtain the desired bioactivity. It was verified that Chalcones and derivatives are promising agents for combating the multidrug resistance of S. aureus to drugs.

The online version contains supplementary material available at 10.1007/s13205-022-03398-7.