The [1,2,4]triazolo[1,5-a]pyrimidines (TPs) comprise an important class of non-naturally occurring small molecules that aroused the interest of researches. This scaffold is present in diverse important structures in agriculture and medicinal chemistry, such as antibacterial, antifungal, antiviral, antiparasitic, and anticancer. As over the decades the development of the chemistry and application of

The study investigated the anti-urease and cytotoxic activities of two major essential oil compounds; 1-Nitro-2-phenylehtane (NPE) and Nerolidol, isolated from the acetone extract of Dennettia tripetala (Pepper Fruit) seeds. Structural characterization of these compounds was performed by NMR, E1MS, and FT-IR spectroscopic techniques. Anti-urease activity of the compounds on Jack bean Urease was accessed

A novel series of N-methyl/benzyl-substituted benzimidazolyl-linked para-substituted benzyl-based compounds containing 2,4-thiazolidinediones, dimethyl malonate (DMM), and diethyl malonate (DEM) 17–27 were designed, docked, synthesized, and evaluated for their antidiabetic activity studies. Structures of all the synthesized compounds were confirmed through 1H NMR, 13C NMR, FTIR, and mass spectrometry

The water-soluble sulfated derivatives, apigenin-8-sulfonate sodium (AS) and apigenin-3′, 8-disulfonate sodium (ADS) derived from parent apigenin (AP), were synthesized and characterized by infrared (IR) spectra, hydrogen nuclear magnetic resonance (1H NMR), carbon nuclear magnetic resonance (13C NMR), high-resolution mass spectra (HRMS), and elemental analysis. The mice model of hepatotoxicity induced

α-Glucosidase plays a major role in degradation of carbohydrates to glucose. Therefore, inhibition of this enzyme can be useful in the treatment of carbohydrate-related diseases such as diabetes, cancer, and viral infections. In this study, a new series of acridine-9-carboxamide linked to 1,2,3-triazole-N-phenylacetamide derivatives 5a–m were designed, synthesized, and evaluated as potent α-glucosidase

Saponins are a class of amphipathic glycosides prevalent in various plant species. They are very important for human health and may be used in various drug formulations. Saponins play vital roles in inhibition of many singling pathways such as PI3K/AKT pathway, AKT/MAPK pathway, EGFR/PI3K/AKT pathway, PI3K/AKT/mTOR pathway, and RNF6/AKT/mTOR pathway. They have been reported to exhibit cytotoxic activities

A new series of naphthyl chalcones (3a–3p) and their pyrazoline derivatives (4a–4h) were synthesized using substituted acetophenones, substituted naphthaldehydes, and hydrazine hydrate as starting materials. All the synthesized compounds were characterized by IR, NMR, and mass spectrometric analysis and screened for antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC 27924) and

Novel unsaturated piperazine and homopiperazine derivatives (3a–h) were synthesized in medium to good yields by acylation reactions of piperazine and homopiperazine with methacrylic anhydride (2a) and benzoyl chloride (2b). Piperazine containing dihydrofuran compounds (5a–l) were obtained from radical addition and cyclizations of 3a–h with 1,3-dicarbonyl compounds such as dimedone (4a), ethyl acetoacetate

In this study, we synthesize 2-amino-4-alkyl/aryl-6-(hydroxymethyl)-8-oxopyrano[3,2-b] pyran-3-carbonitriles derivatives using a multicomponent reaction featuring aromatic or aliphatic aldehydes, kojic acid, and malononitrile catalyzed by nano fluoroapatite doped with Si and Mg (Si–Mg–FA). All reactions were carried out in EtOH as the solvent under reflux and green condition. The process demonstrates

A series of some novel (E)-2-methyl/propyl-4-[(2-(substitutedbenzylidene)hydrazinyl]-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines was synthesized and characterized by adopting an appropriate synthetic scheme. The effect of electron withdrawing and electron donating groups at the aromatic ring in presence of methyl and propyl substituents at the 2-position of the scaffold was evaluated for anthelmintic

In this work we report the structure–affinity relationships, binding properties, and metabolic stability studies of a series of benzo[d]thiazol-2(3H)one as sigma receptor (σR) ligands. Specifically, to improve the metabolic stability of the cyclic amine fragment of our lead compound (SN56), the metabolically unstable azepane ring was replaced with a 1-adatamantamine moiety. Within the synthesized analogs

Pseudotrachydium kotschyi is a native medicinal plant used as a local medicine from Lorestan province of western Iran having numerous biological properties. After GC−MS analysis of Pseudotrachydium kotschyi essential oils (PKEOs), some biological activities were investigated. Additionally, TNF-α and TGF-β1 were studied in Leishmania-infected macrophages (in vitro) and Carrageenan-induced paw edema

The synthesis and screening of several fusaric acid (FA) and analogues against five common clinical pathogens (gram-positive and gram-negative) and in vitro hemolytic activity assay in human red blood cells, for the first time, were reported. The biological results reveal that FA and its analogues exhibited moderate antimicrobial activities. Compounds 2–5 and 7 showed growth inhibitory activity in

Epilepsy is one of the most common neurological disorders worldwide and it requires a long-term or life-long treatment. Current standard treatment includes the use of antiepileptic drugs. To date, many organic compounds have been synthesized by chemists as potential antiepileptic drugs and their anticonvulsant properties have been investigated. While evaluating the anticonvulsant activities of these

A series of derivatives of 5-hydroxyalkylamino-1,3-oxazoles were synthesized. Among these derivatives, 5 compounds have been evaluated for their activities against a normal laboratory human cytomegalovirus (HCMV) strain, AD169, in human foreskin fibroblast (HFF) cells. Bioassays showed that among these, 2 compounds containing a remainder of glucamine exhibited moderate antiviral activity (compounds

Bioisosteric replacements are often tried goaling to affect the lipophilicity, polarity, and aqueous solubility of the substances, as a way to obtain therapeutically improved medicines. Also, hydrazonyl compounds are described with a wide range of pharmacological activities, having also recognized activities in antimycobacterial field. In this study, twenty-seven pyrimidinyl and pyrazinyl derivatives

A novel library of chalcone linked thiazole-imidazopyridine (12a–j) derivatives were designed, synthesized, and their structures were characterized by 1H NMR, 13C NMR and mass spectral studies. Further, all compounds were tested for their anticancer effects on four human cancer cell lines including MCF-7 (breast carcinoma), A549 (lung carcinoma), DU-145 (prostate carcinoma) and MDA MB-231 (breast carcinoma)

Three esters of rhodamine B (1–3) differing in their alkyl chain lengths as well as several rhodamine B amides (4–9) were synthesized in good yields and tested for their cytotoxicity in SRB assays employing several human tumor cell lines. The rhodamine B esters were unselective but showed cytotoxicity of as low as EC50 = 0.15 ± 0.02 µM. The rhodamine B amides were slightly less cytotoxic but showed

Cancer is often associated with chronic inflammation. In order to develop potential anticancer and anti-inflammatory agents a series of 26 diarylidenecyclopentanones (DACPs) Ia–Iv, II, III, and IV were synthesized. Five of the synthesized DACPs are novel (Ih, Ij, Ik, Is, and Iv), derivative Iv was characterized using single-crystal X-ray diffraction study. All the synthesized derivatives were tested

N-alkylated and O-alkylated anthraquinone derivatives with structures analogous to mitoxantrone were synthesized, characterized, and evaluated for their cytotoxic properties against three tumor cell lines (Human Breast Adenocarcinoma MCF-7, Human Cervical Adenocarcinoma HeLa, and Human Glioblastoma M059J) and a normal cell line (human lung fibroblasts GM-07492A). A structure-activity relationship study

Leishmaniasis is a severe disease caused by protozoa of the genus Leishmania. The disease affects millions of people. Treatment is limited to only a few drugs that cause severe side effects. The identification of new compounds to treat leishmaniasis remains a challenge. This study aimed to determine the chemical composition of Eugenia moraviana fruit extract (EmCE) and to investigate its effect on

A library of indolinedione–coumarin hybrid molecules was rationally designed and synthesized against hyperuricemia. All of the synthesized hybrid molecules were tested to check their inhibitory activity against xanthine oxidase enzyme by using a spectrophotometric assay. The results revealed that the compound showed IC50 values within the range of 6.5–24.5 µM amongst which compound K-7 was found to

To continue the research on the preparation of resveratrol structural analogs containing the 3-pyridinol fragment, a series of derivatives with an ethyl radical sterically shielding the hydroxyl group was synthesized. It was shown that the ethyl group introduction has an ambiguous effect on the radical scavenging and antioxidant properties of the stilbazoles studied, which is probably related to the

We are aiming in this work to synthesize target molecules not only possess antitumor activities but also kinase inhibitors. The target molecules were obtained from dimedone, which reacted with triethoxymethane to produce a product that is capable for many heterocyclization reactions to give fused pyrazole, thiophene and isoxazole derivatives. Compounds 7b, 7c, 7d, 9b, 11, 12c, 12d, 14b, 16b, 17c, 17d

The aberrant protein–protein interaction between calmodulin and mutant huntingtin protein in Huntington’s disease patients has been found to contribute to Huntington’s disease progression. A high-throughput screen for small molecules capable of disrupting this interaction revealed a sultam series as potent small-molecule disruptors. Diversification of the sultam scaffold afforded a set of 24 analogs

The most common mechanism of the resistance to β-lactam antibiotics is the expIdentification of cisplatin and palladiuression of β-lactamases, which can hydrolyze the β-lactam moiety and deactivate these antimicrobials. The worldwide prevalence of New Delhi metallo-β-lactamase-1 (NDM-1), also known as carbapenemase has created distress among clinicians. NDM-1 is a type of metallo β-lactamase (type

A series of (E)-1,2-diarylethylidenehydrazine carboximidamides 2a–j were synthesized and characterized by NOESY experiment as anticonvulsant agents and their antiseizure activity was evaluated by intracerebroventricular administration of compounds. Most of the compounds had significant protection against tonic-clonic seizures and 2a was found to be as equipotent as carbamazepine in seizures control

A series of new C28-amino-lupanes bearing A-azepano- and A-seco-3-amino-fragments was synthesized from 3,28-dioximino-betulin and evaluated for cytotoxicity toward the NCI-60 cancer cell line panel and antimicrobial activity against key ESKAPE pathogens. A-azepano-28-amino-betulin exhibited remarkable activities with GI50 ranging from 1.16 to 2.27 μM against all panel with the highest activity toward

We previously reported a series of p53-elevating anthraquinone compounds with considerable cytotoxicity for acute lymphoblastic leukemia (ALL) cells. To further develop this class of compounds, we examined the effect of a few key structural features on the anticancer structure–activity relationship (SAR) in ALL cells. The active analogs showed comparable cytotoxicity and upregulation of p53 but did

To achieve the full potential of pharmacogenomics, one must accurately predict the functional outcomes that arise from amino acid substitutions in proteins. Classically, researchers have focused on understanding the consequences of individual substitutions. However, literature surveys have shown that most substitutions were created at evolutionarily conserved positions. Awareness of this bias leads

Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with metabolic disruption and nonalcoholic fatty liver disease (NAFLD). Based on their ability to activate the aryl hydrocarbon receptor (AhR), PCBs are subdivided into two classes: dioxin-like (DL) and non-dioxin-like (NDL) PCBs. Previously, we demonstrated that NDL PCBs compromised the liver to promote more severe diet-induced

Cancer is a major worldwide public health problem and is still the leading cause of death in the United States. There are many types of cancer treatment but completely successful results are oftentimes not attained. It remains a challenge to develop efficacious clinically useful cancer therapies. Therapies targeting dysregulated signal transduction pathways in cancer can be efficacious anti-cancer

The potentiation of p53 activity through inhibition of its negative regulator MDM2 is an attractive strategy for anticancer therapy. Much progress has been made in the last decade in a diverse range of areas related to p53 and MDM2. This review focuses on the recent progress in developing small-molecule inhibitors of the MDM2 protein by covering the following approaches that inhibit the function of

Modification of endogenous proteins by drugs and drug metabolites are thought to be a cause of idiosyncratic adverse drug reactions (IADRs). Trimethoprim (TMP) is a commonly prescribed antibiotic that has been implicated in IADRs; however, there is no known mechanism by which this drug or its metabolites modify proteins. This study describes the results of screening trimethoprim and its primary metabolites

The targeted delivery of cytotoxic agents to prostate cancer cells via selective activation of peptide-linked prodrugs by prostate-specific antigen (PSA) has been previously demonstrated. In our continued efforts to design prodrugs with improved prostate tumor specificity, we developed GABA ← mGly-Ala-Ser-Chg-Gln and glutaryl-Ser-Ala-Ser-Chg-Gln as promoieties with enhanced PSA specificity starting

We report the comparison of two small-molecule collections synthesized at KU at two different eras. We used a machine learning tool to classify the compounds in these collections by their predicted protein targets. The analyses shine light on the evolution of medicinal chemistry research at the University of Kansas, and reveal several new associations between compounds and protein targets.

In our continued efforts to develop targeted prodrugs activated by prostate-specific antigen (PSA), we designed and synthesized novel phosphoramide mustard peptide conjugates using previously optimized PSA substrates. Initial Nu/Nu mouse PK studies indicated that prodrug I (glutaryl-Hyp-Ala-Ser-Chg-Gln-NH-2-F-Bn-phosphoramide mustard) exhibits high clearance with significant extrahepatic metabolism

A series of 2,3-diaryldibenzo[b]thiophene derivatives have been synthesized via Suzuki coupling reactions in moderate to good yields (59–79%). The synthesized compounds were evaluated for their antithrombolytic, biofilm inhibition, and hemolytic potential. All compounds showed significant biological potential. Compound (4k) revealed excellent antithrombolytic (87.24%) and biofilm inhibition (99.64%)

Lippia graveolens is a plant used for a variety of medicinal purposes and as a seasoning. Chemical investigation of a methanol extract obtained by percolation of its leaves and flowers led to the isolation of two monoterpenes (1–2) and twelve flavonoids, including two flavonols (3–4), two flavones (5–6), four flavanones (7–10), two dihydroflavonols (11–12), and two dihydrochalcone glucosides (13–14)

The membrane-embedded γ-secretase complex carries out hydrolysis within the lipid bilayer in proteolyzing nearly 100 different membrane protein substrates. Among these substrates, the amyloid precursor protein (APP) has been the most studied, as generation of aggregation-prone amyloid β-peptide (Aβ) is a defining feature of Alzheimer’s disease (AD). Mutations in APP and in presenilin, the catalytic

A series of hydroxy-, oximino-, lactame, arylidene, N-methylpiperazinyl amide, isoxazole, pyrimidine derivatives of dipterocarpol, quinopimaric, and dammarenolic acids were synthesized and evaluated for cholinesterase inhibitory activity and cytotoxicity. All of the compounds were weak inhibitors for the enzyme acetylcholinesterase while being no inhibitor for butyrylcholinesterase. Dihydroquinopimaric

Research over the past half-century has demonstrated that the metabolism of drugs and other foreign compounds to chemically reactive intermediates that bind covalently to endogenous proteins can, in certain cases, lead to organ damage or to immune-mediated adverse reactions. While the chemistry of metabolic activation is now relatively well understood, the molecular events that link exposure to reactive

A single protein-binding pocket often times binds to a diverse range of ligands with distinct structural features. Understanding the structural correlations of the different ligands remains a major challenge in medicinal chemistry research. We recently developed the template-based alignment modeling (TAM) method as a simple yet effective approach for understanding structure–activity relationships (SARs)

Grapefruit-mediated fruit–drug interaction has been well discussed in clinical practice. However, the biochemical mechanisms for such interaction are far beyond our understanding. The objectives of the present study aimed at the interaction between bergaptol (BGT) and CYP2C9. BGT, one of the major furanocoumarin constituents in grapefruit, has been reported to inhibit the activity of CYP2C9. And a

In an effort to develop potent anti-influenza drugs that inhibit the activity of influenza virus RNA-dependent RNA polymerase (IAV RdRp), a database of nucleoside triphosphates with ~800 molecules were docked with the homology model of IAV RdRp from A/PR/8/34/H1N1 strain. Out of top 12 molecules that bind with higher affinities to the catalytic site of IAV RdRp above and below the PB1 priming loop

Nigella glandulifera Freyn et Sint (N. glandulifera) is frequently added to naan (a kind of crusty pancake and a favorite food of the Uyghur and Kazak people) as a spice. The water decoction of N. glandulifera was used as traditional Uighur medicine to treat tinnitus, amnesia, amenorrhea, hypogalactia, heat stranguria, urethral calculus, alopecia and hair-blacking, edema, and bronchial asthma. This

The 7-azaindole scaffold attracts attention due to its value in the design of inhibitors of diseases related protein kinases. However, this scaffold has not been evaluated against Haploid germ cell-specific nuclear protein kinase (Haspin). Herein, we report the synthesis of a select set of 7-azaindole derivatives and their evaluation against Haspin. The compounds were also evaluated against CDK9/Cyclin

Inflammation is an important, normal, and complex host defense response to injury, autoimmune responses or infectious agents. However, chronic inflammation is associated with diseases like rheumatoid arthritis, cancers, cardiovascular diseases, diabetes, and obesity, and over 60% of deaths worldwide. Interleukine-6 is one of the key proinflammatory cytokines involved in inflammation processes and therefore

A hybrid pharmacophore approach was applied to design and synthesize a series of benzo[b]thiophene-diaryl urea derivatives 17a–g with potential anticancer effect. In vitro antiproliferative activities of all target compounds were evaluated against HT-29 and A549 cancer cell lines. Three compounds 17b, 17d, and 17f exhibited antiproliferative activities on both cell lines comparable to that of the positive

The diaryl ureas are very important fragments in medicinal chemistry. By means of computer-aided design, 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives were designed and synthesized, and evaluated for their antiproliferative activity against A549, HCT-116, PC-3 cancer cell lines, and HL7702 human normal liver cell lines in vitro by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium

This communication describes a variety of nucleophilic ring openings of N-arylated oxathiazinane heterocycles. We find that this reaction is compatible with phenoxides, naphthoxides, and thiolates and allows for the rapid assembly of N-aryl-amino ethers and N-aryl-amino thioethers. Fourteen examples are shown and a mechanistic pathway is hypothesized.

Eighteen novel N-2,4-dimethoxyphenyl dithiolopyrrolone derivatives inhibiting bacterial RNA polymerase (RNAP) were synthesized based on dithiolopyrrolone scaffold. Some compounds displayed potent antimicrobial activity against Gram-positive bacteria of Staphylococcus aureus and Streptococcus pneumoniae, but not the Gram-negative bacteria of Escherichia coli and Pseudomonas aeruginosa. Moreover, the

The role of mast cells can be protective or harmful; depending upon the physiological/pathological condition in which they get activated. The latter role is due to mast cell degranulation and release of an array of incendiary mediators. Mast cells have a well-established role in diseases like allergy, eczema, anaphylactic shock, mastocytosis, and other miscellaneous mast cell diseases. Previously,

Infectious diseases such as tuberculosis and leishmaniasis are leading causes of human death. One of the major factors contributing to the poor control of these diseases is primarily the reduced effectiveness of the existing chemotherapies as result of the increasing rise of multidrug-resistant strains of their causative agents. This leads to the imperative need to develop new and effective drugs.

This article reports the diastereoselective synthesis of some novel naphthalimido and bis-naphthalimido β-lactam derivatives and a preliminary evaluation of their anticancer properties. The reactions were completely diastereoselective, leading exclusively to the formation of cis-β-lactams 11a–l and trans-bis-β-lactams 16a–g. All of these compounds were obtained in good to excellent yields and their

Gibberellic acid (GA3) is a tetracyclic diterpene compound which displays interesting bioactivities. Recently, its potential use for preparing antitumor drug leads has been highlighted, and various modification methods of GA3 have been reported. Aiming at investigating GA3 derivatives with potential antitumor activities, ring distortion of GA3 under different conditions was carried out, and this was

In this study, we report the synthesis and biological evaluation of a variety of α- and β-hydroxy substituted amino acid derivatives as potential amino acid subunits in inhibitors of GABA uptake transporters (GATs). In order to ensure that the test compounds adopt a binding pose similar to that presumed for related larger GAT inhibitors, lipophilic residues were introduced either at the amino nitrogen

The skin is an important barrier against environmental factors. Foregoing studies has shown that human KLK7 is a protease which promoted epidermal shedding, affected the epidermal barrier and increased the risk of atopic dermatitis. In this study, the structure and activity relationship of 40 human KLK7 inhibitors was explored by three-dimensional quantitative structure–activity relationship (3D-QSAR)

Nowadays, the emergence of superbugs is one of the most serious public health problems. Strains of Staphylococcus aureus and Klebsiella pneumoniae, resistant to many antimicrobials available in clinical practice, have become increasingly common. The development of new drugs for the treatment of infections caused by these pathogens is necessary and urgent. A series of 11 analogs of marine 3-alkylpyridine

In targeted therapy of breast cancer, human epidermal growth factor receptor 2 HER2 (PDB ID: 3PP0) is being considered as a promising route to design novel anti-breast cancer drugs. In this work, we report two of novel N-substituted pyrrolidine at C-8 position of quinolone derivatives 18 and 19, their synthesis under microwave technique, spectral methods, molecular docking study and anti-HIV activities