Antiparasitic Activities of Acyl Hydrazones from Cinnamaldehydes and Structurally Related Fragrances.

New drugs for the treatment of protozoal parasite infections such as toxoplasmosis and leishmaniasis are required. Cinnamaldehyde and its derivatives appear to be promising antiparasitic drug candidates. Acyl hydrazones of cinnamaldehyde, 4-dimethylaminocinnamaldehyde, and of the synthetic fragrances silvial and florhydral were prepared and tested for activity against () and () parasites.

Superior Anticancer and Antifungal Activities of New Sulfanyl-Substituted Niclosamide Derivatives.

The approved anthelmintic salicylanilide drug niclosamide has shown promising anticancer and antimicrobial activities. In this study, new niclosamide derivatives with trifluoromethyl, trifluoromethylsulfanyl, and pentafluorosulfanyl substituents replacing the nitro group of niclosamide were prepared (including the ethanolamine salts of two promising salicylanilides) and tested for their anticancer activities against esophageal adenocarcinoma (EAC) cells. In addition, antifungal activity against a panel of strains, the most abundant causative agent of the neglected tropical disease eumycetoma, was evaluated.

A New Synthetic Curcuminoid Displays Antitumor Activities in Metastasized Melanoma.

Aim: The semisynthetic derivatives MePip-SF5 and isogarcinol, which are aligned with the natural products curcumin and garcinol, were tested for their antitumor effects in a preclinical model of pulmonary melanoma metastasis.

Methods And Results: MePip-SF5 was almost five times more effective in inhibiting B16F10 melanoma cell proliferation than its original substance of curcumin (IC MePip-SF5 2.8 vs.

Analogs of the Catechol Derivative Dynasore Inhibit HIV-1 Ribonuclease H, SARS-CoV-2 nsp14 Exoribonuclease, and Virus Replication.

Viral replication often depends on RNA maturation and degradation processes catalyzed by viral ribonucleases, which are therefore candidate targets for antiviral drugs. Here, we synthesized and studied the antiviral properties of a novel nitrocatechol compound () and other analogs that are structurally related to the catechol derivative dynasore. Interestingly, compound strongly inhibited two DEDD box viral ribonucleases, HIV-1 RNase H and SARS-CoV-2 nsp14 3'-to-5' exoribonuclease (ExoN).

Fluorinated and -Acryloyl-Modified 3,5-Di[()-benzylidene]piperidin-4-one Curcuminoids for the Treatment of Pancreatic Carcinoma.

Pancreatic carcinoma is a cancer disease with high mortality. Thus, new and efficient treatments for this disease are badly needed. Curcumin has previously shown promising effects in pancreatic cancer patients; however, this natural compound suffers from inadequate efficacy and bioavailability, preventing its clinical approval.

Palladium and Platinum Complexes of the Antimetabolite Fludarabine with Vastly Enhanced Selectivity for Tumour over Non-Malignant Cells.

The purine derivative fludarabine is part of frontline therapy for chronic lymphocytic leukaemia (CLL). It has shown positive effects on solid tumours such as melanoma, breast, and colon carcinoma in clinical phase I studies. As the treatment of CLL cells with combinations of fludarabine and metal complexes of antitumoural natural products, e.

Versatile anti-infective properties of pyrido- and dihydropyrido[2,3-d]pyrimidine-based compounds.

A series of 1H-indeno[2',1':5,6]dihydropyrido[2,3-d]pyrimidine and 1H-indeno[2',1':5,6]pyrido[2,3-d]pyrimidine derivatives was prepared and screened for antiparasitic and viral RNase H inhibitory activity. Several compounds showed considerable activity against Toxoplasma gondii parasites and Leishmania major amastigotes, which warrants further investigation. Based on the structural similarities of certain derivatives with common viral RNase H inhibitors, a HIV-1 RNase H assay was used to study the RNase H inhibition by selected test compounds.

Targeting Colon Cancer Cells with Pyrazino-Imidazolinone Derivatives: Synthesis, Molecular Docking, and in Vitro Evaluation of Anti-Proliferative and Pro-Apoptotic Activities.

We report the synthesis, spectroscopic characterization, molecular docking and biological evaluation of nine pyrazino-imidazolinone derivatives. These derivatives were evaluated for their anticancer activity against three cancer cell lines: 518A2 melanoma, HCT-116, and HCT-116 p53 knockout mutant colon carcinoma. The MTT assay was employed to assess their effectiveness.

Regiospecific Reduction of 4,6-Dinitrobenzimidazoles: Synthesis, Characterization, and Biological Evaluation.

The regiospecific reduction of 4,6-dinitrobenzimidazole derivatives leading to the corresponding 4-amino-6-nitrobenzimidazoles was studied. The identification of the formed product structures was accomplished by spectroscopic and X-ray diffraction data. The anticancer and antiparasitic activities of the synthesized compounds were examined, and promising activities against Toxoplasma gondii and Leishmania major parasites were discovered for certain 4,6-dinitrobenzimidazoles in addition to moderate anticancer activities of the 4-amino-6-nitrobenzimidazole derivatives against T.

Anti-Tumoural [NHC(thiolato)] Gold(I) Complexes Derived from HIF-1α Inhibitor AC1-004 Target the Mitochondrial Redox System and Show Antiangiogenic Effects in vivo.

AC1-004 is a potent inhibitor of the hypoxia-inducible factor alpha (HIF-1α) pathway, essential for tumour growth, angiogenesis and metastasis. We modelled a series of gold(I) complexes on AC1-004, retaining its 5-carboalkoxybenzimidazole as an NHC ligand while replacing its 2-aryloxymethyl residue with modified thiolato gold(I) fragments. The intention was to augment a potential HIF-1α inhibition by conducive effects typical of NHC gold complexes, such as an inhibition of tumoural thioredoxin reductase (TrxR), an increase in reactive oxygen species (ROS), and cytotoxic and antiangiogenic effects.

Multimodal 4-arylchromene derivatives with microtubule-destabilizing, anti-angiogenic, and MYB-inhibitory activities.

Efficient and readily available anticancer drugs are sought as treatment options. For this reason, chromene derivatives were prepared using the one-pot reaction and tested for their anticancer and anti-angiogenic properties. 2-Amino-3-cyano-4-(aryl)-7-methoxy-4H-chromene compounds (2A-R) were repurposed or newly synthesized via a three-component reaction of 3-methoxyphenol, various aryl aldehydes, and malononitrile.

Evaluation of the Antiparasitic and Antifungal Activities of Synthetic Piperlongumine-Type Cinnamide Derivatives: Booster Effect by Halogen Substituents.

A series of synthetic N-acylpyrrolidone and -piperidone derivatives of the natural alkaloid piperlongumine were prepared and tested for their activities against Leishmania major and Toxoplasma gondii parasites. Replacement of one of the aryl meta-methoxy groups by halogens such as chlorine, bromine and iodine led to distinctly increased antiparasitic activities. For instance, the new bromo- and iodo-substituted compounds 3 b/c and 4 b/c showed strong activity against L.

Formal synthesis of kibdelomycin and derivatisation of amycolose glycosides.

A convergent total synthesis of bacterial gyrase B/topoisomerase IV inhibitor kibdelomycin (a.k.a.

New 4,5-Diarylimidazol-2-ylidene-iodidogold(I) Complexes with High Activity against Esophageal Adenocarcinoma Cells.

Inspired by the vascular-disrupting agent combretastatin A-4 and recently published anticancer active -heterocyclic carbene (NHC) complexes of Au(I), a series of new iodidogold(I)-NHC complexes was synthesized and characterized. The iodidogold(I) complexes were synthesized by a route involving van Leusen imidazole formation and -alkylation, followed by complexation with AgO, transmetalation with chloro(dimethylsulfide)gold(I) [Au(DMS)Cl], and anion exchange with KI. The target complexes were characterized by IR spectroscopy, H and C NMR spectroscopy, and mass spectrometry.

New Functional Polymer Materials via Click Chemistry-Based Modification of Cellulose Acetate.

Cellulose acetate (CA) was partially acrylated, and the resulting cellulose acetate acrylate (acryl-substitution degree of 0.2) underwent quantitative thio-Michael click reactions with various thiols. A toolbox of functional CA polymers was obtained in this way, and their properties were studied.

Syntheses and Antibacterial Evaluation of New Penicillium Metabolites Gregatins G and Thiocarboxylics C.

Two pairs of side-chain epimeric 3-methoxycarbonyl-dihydrofuran-4-ones with structures purported for thiocarboxylics C and gregatins G , isolated from Penicillium sp. Sb62, were synthesised for the first time in five steps and 17-25 % yield. Key steps were a Suzuki cross-coupling, a Yamaguchi esterification, and a base-induced Knoevenagel-type condensation.

Divergent Synthesis of Six Recent Berkeleylactones.

The six recently isolated berkeleylactones E, J, K, M, N, and O were synthesized for the first time by a divergent strategy starting from a common intermediate in our synthesis of berkeleylactone A. Key features were the stereoselective formation of the γ,δ-dihydroxy-α,β-unsaturated ester moiety and the development of a general protection group strategy. Along the way we also established a short high-yielding formal synthesis of the often-synthesized antibiotic A26771B.

Antiparasitic Activity of Fluorophenyl-Substituted Pyrimido[1,2-]benzimidazoles.

A series of fourteen pyrimido[1,2-]benzimidazole compounds was prepared by straightforward heterocyclic chemistry and oxidation methods. The new pyrimidobenzimidazole derivative with a 3-fluorophenyl substituent was identified as a new antiparasitic compound showing excellent activities against parasites. was highly active against promastigotes and amastigotes with EC values in the nanomolar concentration range.

Syntheses and Biofilm Reducing Effects of l-Dopa-Derived Analogues of the Fungal Macrocidins A and Z.

Four analogues of the fungal metabolites macrocidin A and Z, featuring [13]para- or [13]metacyclophanes, were synthesised from fully and orthogonally protected l-dopa instead of l-tyrosine. They were tested for antibiotic activities and for effects on the growth and persistence of microbial biofilms. Tentative structure-activity relationships and distinct differences when compared with the natural lead compounds were identified.

Synthesis and Anticancer Evaluation of New Indole-Based Tyrphostin Derivatives and Their (-Cymene)dichloridoruthenium(II) Complexes.

New -alkylindole-substituted 2-(pyrid-3-yl)-acrylonitriles with putative kinase inhibitory activity and their (-cymene)Ru(II) piano-stool complexes were prepared and tested for their antiproliferative efficacy in various cancer models. Some of the indole-based derivatives inhibited tumor cell proliferation at (sub-)micromolar concentrations with IC values below those of the clinically relevant multikinase inhibitors gefitinib and sorafenib, which served as positive controls. A focus was set on the investigation of drug mechanisms in HCT-116 p53-knockout colon cancer cells in order to evaluate the dependence of the test compounds on p53.

New chimeric HDAC inhibitors for the treatment of colorectal cancer.

Colorectal cancer is the third most common cause of cancer-associated deaths due to a high recurrence rate and an increasing occurrence of resistance to established therapies. This highlights the importance of developing new chemotherapeutic agents. The current study focuses on cancer-specific targets such as apoptosis-inhibiting survivin, which distinguishes cancer cells from healthy tissue.

Synthesis and Bioactivity of Thiocarboxylic A and Derivatives.

The metabolite thiocarboxylic A () and three close analogues were synthesized in 14 steps. The stereogenic elements were installed via stereoselective Sharpless epoxidation, ()-selective reduction of a dibromide, and a Suzuki cross coupling. Thiocarboxylic A () was obtained in 6% overall yield.

A New Naphthopyran Derivative Combines -Myb Inhibition, Microtubule-Targeting Effects, and Antiangiogenic Properties.

Based on the promising -Myb inhibitor , a series of 2-amino-4-aryl-4-naphtho[1,2-]pyran-3-carbonitriles (, -, -) were repurposed or newly synthesized via a three-component reaction of 1-naphthol, and various aryl aldehydes and malononitrile and screened for their -Myb inhibitory activities. also served as a lead compound for seven new naphthopyran derivatives (-), which were cytotoxic with nanomolar IC values, to inhibit the polymerization of tubulin, and to destabilize microtubules in living cells. Especially, the alkyne , originally made for intracellular localization studies using click chemistry, showed an overall high activity in all assays performed.

Trans-[bis(benzimidazol-2-ylidene)dichlorido]platinum(II) complexes with peculiar modes of action and activity against cisplatin-resistant cancer cells.

Three series of cis- and trans-[bis(benzimidazol-2-ylidene)dichlorido]platinum(II) and cis-[(benzimidazol-2-ylidene)(DMSO)dichlorido]platinum(II) complexes were synthesised and screened for cytotoxicity against six human cancer cell lines. Depending on their N-alkyl and 5-alkoxycarbonyl substituents, two-digit nanomolar to single-digit micromolar IC values against cancer cell lines intrinsically resistant to or ill-responding to cisplatin were reached by both cis- and trans-configured complexes. The stability of the complexes under aqueous biotest conditions was shown via H and Pt NMR monitoring to be dependent on their configuration and their N-substituents.

Revisiting the anticancer properties of phosphane(9-ribosylpurine-6-thiolato)gold(I) complexes and their 9H-purine precursors.

New mono- and di-nuclear thio-purine and thio-purine nucleoside gold(I) complexes were synthesized, characterized, and evaluated in vitro for biological activities in comparison to related known purine complexes. By combining known anti-tumoral thio-purines with RPAu moieties as present in auranofin, complexes with enhanced effects and selectivities were obtained, which not only act as cytostatics, but also disrupt tumor-specific processes. Their IC values in cytotoxicity test with tumor cell lines ranged from three-digit nanomolar to single-digit micromolar, revealing a tentative structure-activity relationship (SAR).