A cobalt(II) coordination polymer-derived catalyst engineered temperature-induced semi-reversible single-crystal-to-single-crystal (SCSC) dehydration for efficient liquid-phase epoxidation of olefins.

Single-crystal-to-single-crystal (SCSC) transformations provide more avenues for phase transitions, which have piqued great interest in crystal engineering. In this work, a 3D Co(II)-based coordination polymer (CP), (1), (where (btec) = 1,2,4,5-benzenetetracarboxylate) undergoes SCSC transition upon heating at 180 °C to afford an anhydrous phase (1'). Room-temperature water-vapour induced semi-reversible SCSC transformation of 1' involves condensation of two water molecules coordinating to the metal cluster, yielding a new framework (2).

Enhanced Catalytic Activity of a Copper(II) Metal-Organic Framework Constructed Semireversible Single-Crystal-to-Single-Crystal Dehydration.

Herein, we present a copper(II) metal-organic framework, () [(btec) = 1,2,4,5-benzenetetracarboxylate], that undergoes single-crystal-to-single-crystal transformations into two anhydrous phases and with the chemical formula , triggered by two-step dehydration at 403 and 433 K, respectively. After immersion in water for 3 days at room temperature, transformed into (), while both and took 1 week to revert to . Dynamic vapor sorption studies validated water-induced reversible structural transformations at 70% relative humidity (RH).

Discovery of Novel Thiazolidinedione-Derivatives with Multi-Modal Antidiabetic Activities In Vitro and In Silico.

Diabetes mellitus (DM) and related complications continue to exert a significant burden on health care systems globally. Although conventional pharmacological therapies are beneficial in the management of this metabolic condition, it is still necessary to seek novel potential molecules for its management. On this basis, we have synthesised and evaluated the anti-diabetic properties of four novel thiazolidinedione (TZD)-derivatives.

Hydrazone-Tethered 5-(Pyridin-4-yl)-4H-1,2,4-triazole-3-thiol Hybrids: Synthesis, Characterisation, in silico ADME Studies, and in vitro Antimycobacterial Evaluation and Cytotoxicity.

Compounds containing arylpyrrole-, 1,2,4-triazole- and hydrazone structural frameworks have been widely studied and demonstrated to exhibit a wide range of pharmacological properties. Herein, an exploratory series of new 1,2,4-triazole derivatives designed by amalgamation of arylpyrrole and 1,2,4-triazole structural units via a hydrazone linkage is reported. The synthesised compounds were tested in vitro for their potential activity against Mycobacterium tuberculosis (MTB) H Rv strain.

Synthesis and in vitro antiprotozoal evaluation of novel metronidazole-Schiff base hybrids.

Herein we report the synthesis of 21 novel small molecules inspired by metronidazole and Schiff base compounds. The compounds were evaluated against Trichomonas vaginalis and cross-screened against other pathogenic protozoans of clinical relevance. Most of these compounds were potent against T.

Fluoroquinolone-induced Glycaemic Aberrations: Could Quinolones be Repurposed to Serve as New Antidiabetic Agents?

Nalidixic acid is a synthetic antibiotic discovered in the 1960s during the synthesis of chloroquine, an effective drug for treating malaria. Nalidixic acid became the backbone for developing quinolones that are now widely used clinically for the treatment of various bacterial infections. The mechanism of action of quinolone involves the inhibition of topoisomerase II and topoisomerase IV.

Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency.

A tailored series of coumarin-based ferrocenyl 1,3-oxazine hybrid compounds was synthesized and investigated for potential antiparasitic activity, drawing inspiration from the established biological efficacy of the constituent chemical motifs. The structural identity of the synthesized compounds was confirmed by common spectroscopic techniques: NMR, HRMS and IR. Biological evaluation studies reveal that the compounds exhibit higher in vitro antiparasitic potency against the chemosensitive malarial strain (3D7 ) over the investigated trypanosomiasis causal agent ( 427) with mostly single digit micromolar IC values.

Synthesis of 2-(N-cyclicamino)quinoline combined with methyl (E)-3-(2/3/4-aminophenyl)acrylates as potential antiparasitic agents.

A rationally designed series of 2-(N-cyclicamino)quinolines coupled with methyl (E)-3-(2/3/4-aminophenyl)acrylates was synthesized and subjected to in vitro screening bioassays for potential antiplasmodial and antitrypanosomal activities against a chloroquine-sensitive (3D7) strain of Plasmodium falciparum and nagana Trypanosoma brucei brucei 427, respectively. Substituent effects on activity were evaluated; meta-acrylate 24 and the ortho-acrylate 29 exhibited the highest antiplasmodial (IC  = 1.4 µM) and antitrypanosomal (IC  = 10.

Easy-To-Access Quinolone Derivatives Exhibiting Antibacterial and Anti-Parasitic Activities.

The cell wall of () has a unique structural organisation, comprising a high lipid content mixed with polysaccharides. This makes cell wall a formidable barrier impermeable to hydrophilic agents. In addition, during host infection, resides in macrophages within avascular necrotic granulomas and cavities, which shield the bacterium from the action of most antibiotics.

Design, synthesis and biological evaluation of mono- and bisquinoline methanamine derivatives as potential antiplasmodial agents.

Several classes of antimalarial drugs are currently available, although issues of toxicity and the emergence of drug resistant malaria parasites have reduced their overall therapeutic efficiency. Quinoline based antiplasmodial drugs have unequivocally been long-established and continue to inspire the design of new antimalarial agents. Herein, a series of mono- and bisquinoline methanamine derivatives were synthesised through sequential steps; Vilsmeier-Haack, reductive amination, and nucleophilic substitution, and obtained in low to excellent yields.

Synthesis, Characterization and Biological Activity of Some Dithiourea Derivatives.

Novel dithiourea derivatives have been designed as HIV-1 protease inhibitors using Autodock 4.2, synthesized and characterized by spectroscopic methods and microanalysis. 1-(3-Bromobenzoyl)-3-[2-([(3-bromophenyl)formami-do]methanethioylamino)phenyl]thiourea (10) and 3-benzoyl-1[(phenylformamido)methanethioyl]aminothiourea (12) gave a percentage viability of 17.

The in Vitro Antiplasmodial and Antiproliferative Activity of New Ferrocene-Based α-Aminocresols Targeting Hemozoin Inhibition and DNA Interaction.

The conjugation of organometallic complexes to known bioactive organic frameworks is a proven strategy revered for devising new drug molecules with novel modes of action. This approach holds great promise for the generation of potent drug leads in the quest for therapeutic chemotypes with the potential to overcome the development of clinical resistance. Herein, we present the in vitro antiplasmodial and antiproliferative investigation of ferrocenyl α-aminocresol conjugates assembled by amalgamation of the organometallic ferrocene unit and an α-aminocresol scaffold possessing antimalarial activity.

Synthesis, Structure and In Vitro Anti-Trypanosomal Activity of Non-Toxic Arylpyrrole-Based Chalcone Derivatives.

With an intention of identifying chalcone derivatives exhibiting anti-protozoal activity, a cohort of relatively unexplored arylpyrrole-based chalcone derivatives were synthesized in moderate to good yields. The resultant compounds were evaluated in vitro for their potential activity against a cultured 427 strain. Several compounds displayed mostly modest in vitro anti-trypanosomal activity with compounds and emerging as active candidates with IC values of 4.

Repurposing a polymer precursor: Synthesis and in vitro medicinal potential of ferrocenyl 1,3-benzoxazine derivatives.

Cancer and malaria remain relevant pathologies in modern medicinal chemistry endeavours. This is compounded by the threat of development of resistance to existing clinical drugs in use as first-line option for treatment of these diseases. To counter this threat, strategies such as drug repurposing and hybridization are constantly adapted in contemporary drug discovery for the expansion of the drug arsenal and generation of novel chemotypes with potential to avert or delay resistance.

Anti-Trypanosomal and Antimalarial Properties of Tetralone Derivatives and Structurally Related Benzocycloalkanones.

: Sleeping sickness and malaria alike are insect-borne protozoan diseases that share overlapping endemic areas in sub-Saharan Africa. The causative agent for malaria has developed resistance against all currently deployed anti-malarial agents. In the case of sleeping sickness, the currently deployed therapeutic options are limited in efficacy and activity spectra, and there are very few drug candidates in the development pipeline.

New Quinolone-Based Thiosemicarbazones Showing Activity Against and .

Co-infection of malaria and tuberculosis, although not thoroughly investigated, has been noted. With the increasing prevalence of tuberculosis in the African region, wherein malaria is endemic, it is intuitive to suggest that the probability of co-infection with these diseases is likely to increase. To avoid the issue of drug-drug interactions when managing co-infections, it is imperative to investigate new molecules with dual activities against the causal agents of these diseases.

Quinolone-isoniazid hybrids: synthesis and preliminary cytotoxicity and anti-tuberculosis evaluation.

Herein, we propose novel quinolones incorporating an INH moiety as potential drug templates against TB. The quinolone-based compounds bearing an INH moiety attached a hydrazide-hydrazone bond were synthesised and evaluated against H37Rv (MTB). The compounds were also evaluated for cytotoxicity against HeLa cell lines.

Novobiocin-ferrocene conjugates possessing anticancer and antiplasmodial activity independent of HSP90 inhibition.

A series of tailored novobiocin-ferrocene conjugates was prepared in moderate yields and investigated for in vitro anticancer and antiplasmodial activity against the MDA-MB-231 breast cancer line and Plasmodium falciparum 3D7 strain, respectively. While the target compounds displayed moderate anticancer activity against the breast cancer cell line with IC values in the mid-micromolar range, compounds 10a-c displayed promising antiplasmodial activity as low as 0.889 µM.

Easy-To-Synthesize Spirocyclic Compounds Possess Remarkable in Vivo Activity against Mycobacterium tuberculosis.

Society urgently needs new, effective medicines for the treatment of tuberculosis. To kick-start the required hit-to-lead campaigns, the libraries of pharmaceutical companies have recently been evaluated for starting points. The GlaxoSmithKline (GSK) library yielded many high-quality hits, and the associated data were placed in the public domain to stimulate engagement by the wider community.

Cinnamoyl-Oxaborole Amides: Synthesis and Their in Vitro Biological Activity.

Due to the increased interest in their application in the treatment of infectious diseases, boron-containing compounds have received a significant coverage in the literature. Herein, a small set of novel cinnamoly-oxaborole amides were synthesized and screened against nagana for antitrypanosomal activity. Compound emerged as a new hit with an in vitro IC value of 0.

Expanding the SAR of Nontoxic Antiplasmodial Indolyl-3-ethanone Ethers and Thioethers.

Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by the decreased efficacy of artemisinin combination therapies. Therefore, the development and optimisation of novel antimalarial chemotypes is critical.

Application of the Morita-Baylis-Hillman reaction in the synthesis of 3-[(N-cycloalkylbenzamido)methyl]-2-quinolones as potential HIV-1 integrase inhibitors.

A practicable six-step synthetic pathway has been developed to access a library of novel 3-[(N-cycloalkylbenzamido)methyl]-2-quinolones using Morita-Baylis-Hillman methodology. These compounds and their 3-[(N-cycloalkylamino)methyl]-2-quinolone precursors have been screened as potential HIV-1 integrase (IN) inhibitors. A concomitant survey of their activity against HIV-1 protease and reverse-transcriptase reveals selective inhibition of HIV-1 IN.

Ferrocenyl and organic novobiocin derivatives: Synthesis and their in vitro biological activity.

A focused series of novobiocin derivatives containing a ferrocene unit together with their corresponding organic novobiocin analogues have been synthesized in modest to good yields. These compounds were screened for biological activity against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) and human breast cancer cell line (HCC38). With the exception of compounds 5c and 5d, the general trend observed is that incorporation of the ferrocene moiety into novobiocin scaffold resulted in compounds 6a-d/6f showing enhanced activity compared to organic analogues 5a-b and 5e-f.

Indolyl-3-ethanone-α-thioethers: A promising new class of non-toxic antimalarial agents.

The success of chemotherapeutics in easing the burden of malaria is under continuous threat from ever-evolving parasite resistance, including resistance to artemisinin combination therapies. Therefore, the discovery of new classes of antimalarials which inhibit new biological targets is imperative to controlling malaria. Accordingly, we report here the discovery of indolyl-3-ethanone-α-thioethers, a new class of antimalarial compounds with encouraging activity.

Synthesis and in vitro evaluation of gold(I) thiosemicarbazone complexes for antimalarial activity.

The reaction of thiosemicarbazones (TSCs) with [Au(I)(THT)Cl], THT=tetrahydrothiophene, has been investigated. The resulting gold(I) complexes have been characterized by a range of spectroscopic techniques: NMR spectroscopy, mass spectrometry, microanalysis and infrared spectroscopy. The in vitro antimalarial data for gold(I) TSC complexes suggests that coordination of gold(I) to TSCs enhanced their efficacy against the malaria parasite Plasmodium falciparum and their inhibition of the parasite cysteine protease falcipain-2.