Abstract Excessive cell proliferation due to cell cycle disorders is one of the hallmarks of breast cancer. Cyclin-dependent kinases (CDKs), which are involved in the transition of the cell cycle from G1 phase to S phase by combining CDKs with cyclin, are considered promising targets with broad therapeutic potential based on their critical role in cell cycle regulation. Pharmacological evidence has

Abstract One of the goals of green chemistry is to use environmentally friendly solvents or remove and reduce the volume of harmful spent solvents. In this study, a novel process for the synthesis of 5-substituted 1,3,4-oxadiazole-2-thiol derivatives was proposed via ultrasound-assisted reaction of aryl hydrazides with CS2 (1:1 molar ratio) in some drops of DMF in the absence of basic or acidic catalysts

Abstract Leishmaniasis is one of the most neglected tropical diseases that demand immediate attention to the identification of new drug targets and effective drug candidates. The present study demonstrates the possibility of using threonine synthase (TS) as a putative drug target in leishmaniasis disease management. We report the construction of an effective homology model of the enzyme that appears

Abstract The Corona virus Disease (COVID-19) is caused because of novel coronavirus (SARS-CoV-2) pathogen detected in China for the first time, and from there it spread across the globe creating a worldwide pandemic of severe respiratory complications. The virus requires structural and non-structural proteins for its multiplication that are produced from polyproteins obtained by translation of its

Abstract A series of novel pyrazole-4-carboxamides were rationally designed, synthesized, and their structures were characterized by 1H NMR, 13C NMR and HRMS. Preliminary bioassay showed that four compounds 8g, 8j, 8o and 8s exhibited more than 90% and even completed inhibition against Alternaria solani at 100 μg/mL; and 8d displayed 100% inhibition against Fusarium oxysporum at the same concentration

Thiophene-based analogs have been fascinated by a growing number of scientists as a potential class of biologically active compounds. Furthermore, they play a vital role for medicinal chemists to improve advanced compounds with a variety of biological effects. The current review envisioned to highlight some recent and particularly remarkable examples of the synthesis of thiophene derivatives by heterocyclization

Abstract In this study, an efficient, rapid and simple plant-mediated green sol–gel auto-combustion procedure was presented to synthesis magnesium–cobalt ferrite (MgCoFe2O4) nanocatalyst using an aqueous extract of apple skins as a chelating/combustion agent. The catalyst was assessed by multiple techniques, including FT-IR, XRD, FE-SEM, EDS, elemental mapping, TGA-DTA and VSM. Then, the catalytic

Abstract Spirocyclic compounds fascinate the synthetic chemists due to their privileged ring system and efficacy in drug discovery. Many natural compounds comprise spirocyclic moiety in their skeleton and are effective in pharmaceutical industry. Over the years, many synthetic methodologies have been established for the construction of spirocyclic compounds. In this review, recent synthetic approaches

Abstract A series of ethyl 2-amino-4H-benzo[h]chromene-3-carboxylate derivatives, having phenyl ring with diverse substituents at C4 position of 4H-benzochromene nucleus, were synthesized via one-pot three-component reaction between various aromatic aldehydes, α-naphthol, and ethyl cyanoacetate. The synthesized compounds were screened for their antityrosinase activity. Compound 4i, bearing 4-dimethylamino

Abstract A poor prognosis, relapse and resistance are burning issues during adverse-risk acute myeloid leukaemia (AML) treatment. As a natural medicine, Scutellaria barbata D. Don (SBD) has shown impressive antitumour activity in various cancers. Thus, SBD may become a potential drug in adverse-risk AML treatment. This study aimed to screen the key targets of SBD in adverse-risk AML using the drug–biomarker

Abstract Since the beginning, natural products have represented an important source of bioactive molecules for cancer treatment. Among them, cardenolides attract the attention of different research groups due to their cardiotonic and antitumor activity. The observed biological activity is closely related to their Na+/K+-ATPase inhibition potency. Currently, the discovery of new compounds against cancer

In our study, some newly synthesized aryl-substituted pyrazole derivatives mimicking cis-diphenylethylene scaffold of two apoptotic inducing agents celecoxib and combretastatin A-4 were found to have strong antiproliferative as well as antiinflammatory activities. Among these coxib–combretastatin hybrids, two lead compounds 8 and 6c simultaneously inhibited prostaglandin E2 (PGE2) production in LPS-activated

Abstract The outbreak of SARS-CoV-2 and deaths caused by it all over the world have imposed great concern on the scientific community to develop potential drugs to combat Coronavirus disease-19 (COVID-19). In this regard, lichen metabolites may offer a vast reservoir for the discovery of antiviral drug candidates. Therefore, to find novel compounds against COVID-19, we created a library of 412 lichen

Abstract Practical synthesis and biological activities of quinazolinyl–triazinyl semicarbazides (10a–j) and quinazolinyl–triazinyl thiosemicarbazides (11a–j) have been described. The novel semicarbazides and thiosemicarbazides were prepared by condensation of different nucleophiles like isocyanate and isothiocyanate by the displacement of chlorine atoms on the basis of functionality concept on varying

Abstract Inhibition of Sirtuin2 (SIRT2) protein rescues the α-synuclein toxicity in vitro and in vivo models of Parkinson’s disease (PD). Thioacetyl group can structurally mimic the acetyl group and restrain the deacetylating p53 reaction by SIRT2. This work evaluated the biological activity of designed pentapeptides inhibitor containing N-thioacetyl-lysine against SIRT2. Pentapeptide by introducing

Abstract In the present work, a series of bisbenzazole derivatives were designed and synthesized as antiproliferative agents. The antiproliferative activity of these compounds was investigated using MTT assay. Bisbenzazole derivatives showed significant antiproliferative activity against all the four tested cancer cell lines. Among the various bisbenzazole derivatives, bisbenzoxazole derivatives exhibited

Abstract Chagas disease kills over 10,000 people per year, and approximately 8 million people are infected by Trypanosoma cruzi. The reference drug for treatment of the disease, benznidazole, is the same since the 70s. In recent years, many CYP51 inhibitors were tested against this parasite’s target. One of them, posaconazole, was even tested in clinical trials that unfortunately were not successful

Abstract An efficient, eco-friendly protocol has been described for the chemoselective synthesis of tetracyclic pyrido-fused dibenzodiazepines derivatives via catalyst-free, three-component reaction of dimedone, 1,2-diamines, 3-formylchromones, and malononitrile. The significant advantages of this cascade approach are to create two new rings and four new σ bonds containing three C–N and one C–C bond

Abstract Tuberculosis is one of the leading causes of death across the world. The treatment regimens for tuberculosis are well established, but still the control of the disease faces many challenges such as lengthy treatment protocols, drug resistance and toxicity. In the present work, mycolic acid methyl transferase (MmaA1), a protein involved in the maturation of mycolic acids in the biochemical

In current research, benzazepine derivative is synthesized via a new process of four-component reaction of isatin or its derivatives, α-haloketones, activated acetylenic compounds, isoquinoline and potassium fluoride/clinoptilolite nanoparticles (KF/CP NPs) in acidic solution of H2O2 in water at room temperature. Also, antioxidation property of some prepared benzazepines is investigated by employing

Abstract Urease, a nickel-dependent enzyme, has a powerful catalytic activity to decompose urea into ammonia via hydrolysis reaction under mild condition. In the present work, urease was employed for the synthesis of two series of polyhydroquinoline and polyhydroacridine derivatives via one-pot condensation of the ammonia generated in situ from urea, aryl aldehydes, and dimedone or ethyl acetoacetate

Abstract Antimicrobial resistance has become a significant threat to global public health, thus precipitating an exigent need for new drugs with improved therapeutic efficacy. In this regard, molecular hybridization is deemed as a viable strategy to afford multi-target-based drug candidates. Herein, we report a library of quinoline—1H-1,2,3-triazole molecular hybrids synthesized via copper(I)-catalyzed

Abstract As part of an ongoing effort to develop new anti-tubercular agents, a series of novel indole-fused spirochromene hybrids (7a–l) were efficiently synthesized in excellent yields by the popular ‘Fisher–Indole synthesis’ approach. The structure elucidation of the target compounds was carried out by different spectral techniques including 1H-NMR, 13C-NMR, ESI Mass, and FTIR analysis. Additionally

Abstract Nowadays, application of vinylazides as precursors is a key method for the construction of N-heterocycles in organic synthesis. These versatile three-atom synthons can be converted into intermediates such as 2H-azirines, iminyl radicals, iminyl metal complexes, iminyl inions and nitrilium ions that subsequently afford a wide range of polyfunctional cyclic nitrogen-containing compounds. In

Abstract Chemoselective domino ring opening and selective O/S-alkylation of ethers/thioethers over enol C/O alkylation has been observed. Various 2-aryl chromanones/thiochromanones with alkyl/allyl bromides were smoothly converted into the corresponding highly functionalized ethers and thioethers in excellent yields with high selectivity. Graphic abstract An unusual, chemoselective domino ring opening

According to the fact that 5-nitro-3-trinitromethyl-1H-1,2,4 triazole (NTNMT) is a successful, good explosive, energetic groups such as -CH3, -NH2, -NHNO2, -NO2, -ONO2, -NF2, -CN, -NC, -N3 groups were introduced into NTNMT and their oxygen balance was at about zero. The energetic properties, detonation performance, and sensitivity were studied at the B3LYP/6-31G** level of density functional theory

A multicomponent reaction containing curcumin, aldehydes, malononitrile and amine was developed for the one-pot synthesis of a novel library of 4H-pyran and 1,4-dihyropyridin heterocycles incorporating curcumin moiety. The products were obtained in the presence of p-toluenesulfonic acid as catalyst in ethanol as solvent in good to excellent yields.

The utilization of approved medication is a requisite to combat certain diseases for health; however, the undesirable adverse effects (AEs) due to medication are generally unavoidable. Hypertension is one of such AEs resulting from approved medication in which blood pressure in the arteries gets elevated and is a risk factor for several diseases including heart and kidney failure. HTs are the approved

An efficient synthesis of α-halo-α-arylseleno ketones has been developed via gem-difunctionalization of α-diazoarylketones with diaryldiselenides and N-halosuccinimides. With this multicomponent approach, a series of α-halo-α-arylseleno ketones were accessed in excellent yields and chemoselectivities under mild conditions. This transformation is proposed to proceed via the key intermediate arylselenenyl

Research on anticancer properties of natural compounds, as effective materials that are available while causing minimal side effects, is growing. Ellagic acid (EA) is a well-known polyphenolic compound, which has been found in both free and complex modes in several medicinal plants such as pomegranate, walnut, and berries. Although many articles have reported anticancer properties for this compound

Cerebral amyloid angiopathy (CAA) commonly found in the aged is pathologically characterized by β-amyloid (Aβ) deposition in the walls of arteries and capillaries of brain. In this study, four flexible multidentate benzyldiamine derivatives as potential probes for cerebrovascular Aβ deposition were designed and synthesized. In in vitro inhibition assays, the ligands 18-21 displayed high affinities

A series of novel monocyclic cis-β-lactams were prepared from phenoxyacetic acid as ketene source and imines derived from 1-chloro-3,4-dihydronaphthalene-2-carbaldehyde and respective amine using ethyl 4,5-dichloro-6-oxopyridazine-1(6H)-carboxylate (or 2-ethoxy carbonyl DCPN) as a carboxylic acid activator. This is the first time 2-ethoxy carbonyl DCPN has been used as an acid activator in synthesis

We have created a novel series of mushroom tyrosinase inhibitors with 1,2,4-triazole as fundamental skeleton. The target compound 1,2,4-triazol-3-ylthio)-N-phenyl acetamide derivatives 9(a-l) were synthesized by the reaction of 4- and 5-substituted 1,2,4-triazole-3-thiol derivatives 6(a-c) with 2-chloro-N-sub/un-substituted phenyl acetamide derivatives 8(a-d) under basic condition. By using the analytical

Indole derivatives have been the focus of many researchers in the study of pharmaceutical compounds for many years. Researchers have investigated the effect of carboxamide moiety at positions 2 and 3, giving unique inhibitory properties to these compounds. The presence of carboxamide moiety in indole derivatives causes hydrogen bonds with a variety of enzymes and proteins, which in many cases, inhibits

This study describes the use of 3-aminotriazole, different aldehydes and N-methyl-1-(methylthio)-2-nitroethenamine as a ketene N,S-acetal in a three-component condensation for the synthesis of a novel library of triazolo[1,5-a]pyrimidine scaffolds. The presence of trichloroacetic acid as a Brønsted-Lowry acidic promoter in acetonitrile or water solvent and room temperature condition resulting novel

Reported herein is an unprecedented and sequential three-component synthetic strategy for the preparation of polycyclic N-heterocyclic compounds. This synthetic protocol enabled the preparation of a series of novel nitrogen-containing pentacyclic compound under convenient conditions in excellent yields and short reaction time. The synthesized products were characterized by IR, 1H NMR, 13C NMR and mass

HSV disease is distributed worldwide. Anti-herpesvirus drugs are a problem in clinical settings, particularly in immunocompromised individuals undergoing herpes simplex virus type 1 infection. In this work, 4-substituted-1,2,3-1H-1,2,3-triazole linked nitroxyl radical derived from TEMPOL were synthesized, and their ability to inhibit the in vitro replication of HSV-1 was evaluated. The nitroxide derivatives

Aberrant activation of ERK signaling pathway usually leads to oncogenesis, and small molecular agents targeting this pathway are impeded by the emergence of drug resistance due to reactivation of ERK signaling. Compound DEL-22379 has been reported to inhibit ERK dimerization which was unaffected by drug-resistant mechanism reactivating the ERK signaling. Here, we discussed a structure-activity relationship

A series of thirty-one new compounds were synthesized and evaluated for their anti-HIV-1 and cytotoxicity activity. Of these, twelve were found to be inhibitors of HIV replications in primary human lymphocytes with median effective concentration (EC50) values < 20 µM. However, most of the compounds demonstrated cytotoxicity in different cells. Our structure activity relationship study identified different

An efficient and versatile protocol for the synthesis of hybrid polycyclic quinolinobenzo[a]phenazinones has been developed under SSMR condition via intramolecular domino Knoevenagel-hetero-Diels-Alder reaction involving the generation of two new six membered fused rings and three contiguous stereogenic centers.

This paper presents the efficient synthesis of 2-amino-4H-benzo[b]pyrans using mesoporous poly-melamine-formaldehyde as a polymeric heterogeneous catalyst. According to the principals of green chemistry, the reaction was performed by the planetary ball milling process at ambient and neat conditions. The heterogeneous catalyst could be reused up to five runs with no reducing of catalytic efficiency

In an effort to discover potential cytotoxic agents, a series of novel (Z)-5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)-3-((1-substituted phenyl-1H-1,2,3-triazol-4-yl)methyl)thiazolidine-2,4-dione derivatives (8a-n) were designed and synthesized in various steps with acceptable reaction procedures with quantitative yields and characterized by 1H NMR, 13C NMR, IR, HRMS and ESI-MS spectra. These newly

The preparation of double salt of aluminum sulfate-sulfuric acid (Al4(SO4)6·(H2SO4)·24H2O) by the reaction of aluminum sulfate and sulfuric acid in water is described. Aluminum sulfate-sulfuric acid is characterized via some spectroscopic and microscopic techniques such as infrared spectroscopy (IR), X-ray diffraction spectroscopy (XRD), energy-dispersive X-ray spectroscopy (EDX), scanning electron

Glutaminase plays an important role in carcinogenesis and cancer cell growth. This biological target is interesting against cancer cells. Therefore, in this work, in silico [docking and molecular dynamics (MD) simulations] and in vitro methods (antiproliferative and LC-MS metabolomics) were employed to assay a hybrid compound derived from glutamine and valproic acid (Gln-VPA), which was compared with

Coumarins possess a wide array of therapeutic capabilities, but often with unclear mechanism of action. We tested a small library of 18 coumarin derivatives against human invasive breast ductal carcinoma cells with the capacity of each compound to inhibit cell proliferation scored, and the most potent coumarin analogues selected for further studies. Interestingly, the presence of two prenyloxy groups

4-Thiazolidinones and phenylaminopyrimidines are known as anticancer agents. Imatinib is the pioneer phenylaminopyrimidine derivative kinase inhibitor, which is used for the treatment of chronic myeloid leukemia. With a hybrid approach, a novel series of 5-benzylidene-2-arylimino-4-thiazolidinone derivatives containing phenylaminopyrimidine core were designed, synthesized, and tested for their anticancer

The similarity is an important category in natural sciences. A measure of similarity for a group of various biochemical endpoints is suggested. The list of examined endpoints contains (1) toxicity of pesticides towards rainbow trout; (2) human skin sensitization; (3) mutagenicity; (4) toxicity of psychotropic drugs; and (5) anti HIV activity. Further applying and evolution of the suggested approach

In this study, we applied a direct condensation between 3-acetyl-4-hydroxy-2H-chromen-2-one and different amines (anilines and benzyl amines) in order to synthesize some coumarin-based imines/enamines (3a-o) as cytotoxic agents. All the compounds were characterized by means of FT-IR, NMR, mass spectroscopy and elemental analyses. Since the title compounds can exist as different forms including (s-cis)-imine

In cancer disease, which is one of the problems of today's human societies, the expression of some tyrosine kinase receptors that are effective in the growth and proliferation of cancerous cells rises. Therefore, it is essential to develop and propose new drugs to target the receptors. Performing modeling calculations such as QSAR and docking makes the drug discovery process more efficient. Thus, backpropagation

One palladium-catalyzed sequential coupling reactions were successfully used as a new protocol for the synthesis of unsymmetrical 2,3-diethynyl quinoxalines and 4-ethynyl-substituted pyrrolo[1,2-a]quinoxalines. The one-pot two coupling reactions of 2,3-dichloroquinoxaline, with two different terminal alkynes, under controlled conditions produced selectively unsymmetrical 2,3-diethynyl quinoxalines

The β-glucuronidase, a lysosomal enzyme, catalyzes the cleavage of glucuronosyl-O-bonds. Its inhibitors play a significant role in different medicinal therapies as they cause a decrease in carcinogen-induced colonic tumors by reducing the level of toxic substances present in the intestine. Among those inhibitors, bisindole derivatives had displayed promising β-glucuronidase inhibition activity. In

In an attempt to search for new natural product-based antitumor agents, a series of novel (aryl)methyl-amine derivatives of dehydroabietic acid-based B ring-fused-thiazole were designed and synthesized. The primary bioassay showed that compounds 5r and 5s presented certain inhibitory activity against cancer cells, weak cytotoxic activity against normal cells, and inhibitory activity against PI3K/AKT/mTOR

Abstract A simple and efficient method for the synthesis of dihydro-8H-acenaphtho[1′,2′:4,5]pyrrolo[1,2-a]imidazole-diol derivatives via one-pot, four-component reaction of 1,1-bis(methylthio)-2-nitroethene, various amines, and acenaphthoquinone was developed. All the reactions were carried out in ethanol at reflux without any catalyst. The main advantages of this method are good to high yields, experimental

Abstract Series of novel N-benzyl derivatives of 6-aminoflavone (9a–n) were synthesized and evaluated for anticancer and topoisomerase II enzyme inhibition activity. All the synthesized compounds were screened for in vitro anticancer activity against human breast cancer cell line (MCF-7) and human lung cancer cell line (A-549). Among the synthesized compounds, 9f and 9g were found to be the most potent

Abstract An elastic network model (ENM) represents a molecule as a matrix of pairwise atomic interactions. Rich in coded information, ENMs are hereby proposed as a novel tool for the prediction of the activity of series of molecules, with widely different chemical structures, but a common biological activity. The new approach is developed and tested using a set of 183 inhibitors of serine/threonine-protein

Abstract Microtubule-associated protein tau (MAPT) is a key protein, which is mainly identified as an essential factor for microtubule dynamics and neuronal outgrowth. Though tau has several functions, regulation of insulin signaling is one among them to control type 2 diabetes. Abnormal expression of tau protein leads to hyperphosphorylation and is known as tauopathies. The presence of alloxan occurs

Abstract 2-Naphthol or β-naphthol is an important starting material that has drawn great attention in various organic transformations because of its attributes, such as low cost, easy to handle and eco-friendliness. The electron-rich aromatic framework of 2-naphthol with multiple reactive sites allows it to be utilized in several kinds of organic reactions eventuated to several organic molecules with

Abstract The advent of computational methods for efficient prediction of the druglikeness of small molecules and their ever-burgeoning applications in the fields of medicinal chemistry and drug industries have been a profound scientific development, since only a few amounts of the small molecule libraries were identified as approvable drugs. In this study, a deep belief network was utilized to construct

Abstract Fourteen novel 4,5-diphenyl-imidazol-1,2,3-triazole hybrids 8a–n were synthesized with good yields by performing click reaction between the 4,5-diphenyl-2-(prop-2-yn-1-ylthio)-1H-imidazole and various benzyl azides. The synthesized compounds 8a–n were evaluated against yeast α-glucosidase, and all these compounds exhibited excellent inhibitory activity (IC50 values in the range of 85.6 ± 0

Abstract In the present investigation, a series of dihydrotriazine derivatives-bearing 5-aryloxypyrazole moieties were synthesized and their structures were confirmed by different spectral tools. The biological evaluation in vitro revealed that some of the target compounds exerted good antibacterial and antifungal activity in comparison with the reference drugs. Among these novel hybrids, compound