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The monkeypox virus (MPXV) is an enveloped, double-stranded DNA virus belonging to the genus Orthopox viruses. In recent years, the virus has spread to countries where it was previously unknown, turning it into a worldwide emergency for public health. This study employs a structural-based drug design approach to identify potential inhibitors for the core cysteine proteinase of MPXV. During the simulations, the study identified two potential inhibitors, compound CHEMBL32926 and compound CHEMBL4861364, demonstrating strong binding affinities and drug-like properties. Their docking scores with the target protein were −10.7 and −10.9 kcal/mol, respectively. This study used ensemble-based protein–ligand docking to account for the binding site conformation variability. By examining how the identified inhibitors interact with the protein, this research sheds light on the workings of the inhibitors' mechanisms of action. Molecular dynamic simulations of protein–ligand complexes showed fluctuations from the initial docked pose, but they confirmed their binding throughout the simulation. The MMGBSA binding free energy calculations for CHEMBL32926 showed a binding free energy range of (−9.25 to −9.65) kcal/mol, while CHEMBL4861364 exhibited a range of (−41.66 to −31.47) kcal/mol. Later, analogues were searched for these compounds with 70% similarity criteria, and their IC50 was predicted using pre-trained machine learning models. This resulted in identifying two similar compounds for each hit with comparable binding affinity for cysteine proteinase. This study's structure-based drug design approach provides a promising strategy for identifying new drugs for treating MPXV infections. [ABSTRACT FROM AUTHOR]

Leishmania tropica is a tropical parasite causing cutaneous leishmaniasis (CL) in humans. Leishmaniasis is a serious public health threat, affecting an estimated 350 million people in 98 countries. The global rise in antileishmanial drug resistance has triggered the need to explore novel therapeutic strategies against this parasite. In the present study, we utilized the recently available multidrug resistant L. tropica strain proteome data repository to identify alternative therapeutic drug targets based on comparative subtractive proteomic and druggability analyses. Additionally, small drug-like compounds were scanned against novel targets based on virtual screening and ADME profiling. The analysis unveiled 496 essential cellular proteins of L. tropica that were nonhomologous to the human proteome set. The druggability analyses prioritized nine parasite-specific druggable proteins essential for the parasite's basic cellular survival, growth, and virulence. These prioritized proteins were identified to have appropriate binding pockets to anchor small drug-like compounds. Among these, UDPase and PCNA were prioritized as the top-ranked druggable proteins. The pharmacophore-based virtual screening and ADME profiling predicted MolPort-000-730-162 and MolPort-020-232-354 as the top hit drug-like compounds from the Pharmit resource to inhibit L. tropica UDPase and PCNA, respectively. The alternative drug targets and drug-like molecules predicted in the current study lay the groundwork for developing novel antileishmanial therapies. [ABSTRACT FROM AUTHOR]

This document is an editorial from the journal Frontiers in Chemistry titled "Medicinal chemistry of active pharmaceutical ingredients of drug products." It discusses the importance of active pharmaceutical ingredients (APIs) in drug products and the need for suitable APIs to comply with specific dosage form characteristics. The editorial highlights three research studies related to medicinal chemistry. The first study explores the anti-ulcerative colitis effects of extracts from Calliandra haematocephala. The second study focuses on the quality evaluation of compounds in leaves of six Taxus species. The third study investigates the chemical fingerprinting and biological properties of the essential oil from Eucalyptus globulus leaves. The authors conclude that these studies provide valuable insights into potential therapeutic approaches for various diseases. [Extracted from the article]

Zn:Cr mixed oxide catalyst was examined as an effective and recyclable catalyst for the synthesis selected pyrimidine derivatives in high yield. The catalyst was characterized by FT-IR, XRD, BET, SEM, EDX and Zeta potential analysis. Substituted 4-aryl-6-(3-coumarinyl) pyrimidine-2(1H)-ones were prepared in high yield and purity via the cyclocondensation of urea and 3-acetylcoumarin with substituted aldehydes in the presence of a catalytic amount of Zn:Cr mixed oxide catalyst as Lewis acid at ambient temperature. The effect of the molar ratio of the catalyst was also studied, and as a result, Zn:Cr (10:1) showed better catalytic performance than Zn:Cr (1:1) at identical reaction conditions. Furthermore, catalyst stability was intact as confirmed by the catalyst recyclability experiment. [ABSTRACT FROM AUTHOR]

Here we communicate a method for the synthesis of 4-(4-(piperidin-1-yl)phenyl)-2-thioxo-1,2,3,4-tetrahydro-5H-chromeno[4,3-d]pyrimidin-5-one in one step. The compound was prepared by reacting 4-hydroxy-coumarin, 4-piperidinobenzaldehye, and thiourea in a catalytic quantity of p-toluenesulfonic acid. The novelty of the compound was checked by Sci-finder. The compound was analyzed by NMR spectroscopy (¹H, 13C), and mass spectrometry. The computational studies indicate that the synthesized compound possesses suitable physicochemical properties, drug-likeliness features, and good oral bioavailability. [ABSTRACT FROM AUTHOR]

Reaction of sebacoyl isothiocyanate with cyanoacetic acid hydrazide afforded N1,N10-bis (1,3,4-thiadiazole) derivative which used as key precursor for the preparation of bis (1,3,4-thiadiazolo[3,2-a]pyridine, 4-thiazolidinone, chromene, and naphtho[1,2-b][1,4]oxazine) derivatives. The chemical structures of novel compounds were proven by spectroscopic analyses. [ABSTRACT FROM AUTHOR]

Here we describe the preparation of 2-(4-((1H-benzo[d]imidazol-2-yl)thio)-benzylidene)-hydrazine-1-carbothioamide in two steps. In the first step, 1,3-dihydro-2H-1,3-benzimidazole-2-thione was reacted with 4-fluorobenzaldehyde in DMSO to get 4-[(1H-benzimidazol-2-yl)sulfanyl]benzaldehyde in high yield. The reaction of the obtained aldehyde with thiosemicarbazide in ethanol at reflux temperature yielded 2-({4-[(1H-benzimidazol-2-yl)sulfanyl]phenyl}methylidene)hydrazine-1-carbothioamide. The structure of the synthesized compounds was established by NMR spectroscopy (1H, 13C), mass spectrometry, and infrared spectroscopy. [ABSTRACT FROM AUTHOR]

A new series of 2-imino or 2-oxo-2 H -chromene-6-sulfonamide derivatives 2-9 with potential anti-diabetic activity were designed and synthesized. The new 6-sulfonamide chromenes were synthesized by reacting 3-formyl-4-hydroxybenzenesulfonyl chloride with activated methylene derivatives in the presence of ammonium acetate as a catalyst. The structure of the products was confirmed by spectroscopic analysis. All the designed derivatives 2-9 were evaluated for their activity against α-amylase and exhibited inhibitory percentage values higher than 93% at 100 μg mL -1 . Additionally, the IC 50 values represented a variable degree of activity with two derivatives 2 and 9 exhibiting the most promising derivative results with IC 50 values of 1.76 ± 0.01 and 1.08 ± 0.02 μM, respectively, compared to Acarbose (IC 50 = 0.43 ± 0.01 μM). Additionally, these derivatives showed potency against the α-glucosidase enzyme with IC 50 values of 0.548 ± 0.02 and 2.44 ± 0.09 μg mL -1 , compared to Acarbose (0.604 ± 0.02 μg mL -1 ). Moreover, the in vitro PPAR-γ transactivation assay revealed that chromene-6-sulfonamide derivatives 2 and 9 exhibited potential PPAR-γ activity with IC 50 values of 3.152 ± 0.03 and 3.706 ± 0.32 μg mL -1 , respectively, compared to Pioglitazone (4.884 ± 0.29 μg mL -1 ). This indicates that these derivatives have insulin sensitivity and glucose metabolism activity. The in silico ADMET prediction showed that these derivatives have an acceptable range of oral bioavailability, drug-likeness, and a safe toxicity profile, including being non-cytotoxic, non-mutagenic, non-immunotoxic, and non-carcinogenic. Finally, computational docking analysis demonstrated the ability of these derivatives to interact with α-amylase, α-glucosidase, and PPAR-γ enzymes, with confirmed successful placement due to good binding energy values and various interactions within the pocket., Competing Interests: The authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)