Design, synthesis, and structure-activity relationships of five-membered heterocyclic incorporated aryl(alkyl)azoles: From antiproliferative thiazoles to safer anticonvulsant oxadiazoles.

In the current study, a novel series of 1,2,4-oxadiazoles were designed, synthesized, and evaluated for their biological activities. A cell-based antiproliferative screening was accomplished on the newly synthesized 1,2,4-oxadiazoles along with our previously reported aryl(alkyl)azoles (AAAs) containing middle heterocyclic cores thiazole and oxazole. Among the tested compounds, naphthyl- thiazoles demonstrated higher antiproliferative activity and B3 was identified as the most potent compound with IC values in the range of 2.

Design, synthesis and biological evaluation of (E)-kojyl-styryl-sulfones: Novel recilisib hybrids as promising radioprotectors.

Radioprotectors are synthetic compounds, natural products, or biological agents that are administered before irradiation to protect normal cells against ionizing radiation (IR)-induced injuries. We have designed novel hybrid (E)-kojyl-styryl-sulfones 10a-n by applying the pharmacophore hybridization strategy to combine key structural motifs of the natural antioxidant kojic acid and the emerging radioprotector Ex-RAD (recilisib sodium). These hybrids were successfully synthesized and characterized with (E)-geometry.

Multi-functional tyrosinase inhibitors derived from kojic acid and hydroquinone-like diphenols for treatment of hyperpigmentation: Synthesis and in vitro biological evaluation.

A series of multi-functional tyrosinase inhibitors derived from kojic acid (KA) and hydroquinone-like diphenols were designed and synthesized using click chemistry. The in vitro enzymatic assay revealed that all compounds containing a free enolic structure showed excellent activity against tyrosinase (IC = 0.14-3.

In Vitro Evaluation of Anti-Parasitic Activities of Quinolone-Coumarin Hybrids Derived from Fluoroquinolones and Novobiocin Against Toxoplasma gondii.

Purpose: Toxoplasmosis is caused by the parasite Toxoplasma gondii (T. gondii). In immunocompetent individuals, the infection is often asymptomatic; however, in expectant mothers and those with immune system deficiencies, complications may arise.

Insights into the development of Tc-radioligands for serotonergic receptors imaging: Synthesis, labeling, In vitro, and In vivo studies.

Serotonergic (5-hydroxytryptamine; 5-HT) receptors play critical roles in neurological and psychological disorders such as schizophrenia, anxiety, depression, and Alzheimer's diseases. Therefore, it is particularly important to develop novel radioligands or modify the existing ones to identify the serotonergic receptors involved in psychiatric disorders. Among the 16 subtypes of serotonergic systems, only technetium-99m based radiopharmaceuticals have been evaluated for serotonin-1A (5-HT), serotonin-2A (5-HT), 5-HT heterodimers and serotonin receptor neurotransmitter (SERT).

Synthesis, Sensing Performance and DFT Studies of a Novel Coumarin-based Schiff Base As a Turn-on Fluorescence Probe for Zinc Ion Detection.

The design and development of novel efficient fluorescent chemical sensors for the selective detection of ions is currently of significant importance in supramolecular chemistry. Since zinc is a ubiquitous, indispensable and the second most abundant metal ion in the human body, developing chemosensors that can accurately discriminate between Zn and Cd ions has been a challenge due to their similar properties as they are in the same group of the periodic table. Therefore, a technique to trace and visualize free zinc ions is demanded.

In-vivo efficiency of the novel azole compounds (ATTAF-1 and ATTAF-2) against systemic candidiasis in a murine model.

Background: Antifungal resistance is the main health concern in the control of invasive fungal infections. This research was designed to further assess the antifungal activity of aryl-1,2,4-triazole-3-ylthio analogs of fluconazole (ATTAFs) against Candida albicans systemic candidiasis in the murine model.

Materials & Methods: The murine model of systemic candidiasis was designed via the inoculation of 1 × 10 CFU of Candida albicans.

Conversion of antibacterial quinolone drug levofloxacin to potent cytotoxic agents.

Levofloxacin, the optical S-(-) isomer of ofloxacin, is a broad-spectrum antibacterial agent widely used to control various infections caused by Gram-positive and Gram-negative bacteria. While the COOH group is necessary for antibacterial activity, its modification can offer anticancer activity to the fluoroquinolone framework. Therefore, several levofloxacin carboxamides 11a-j and 12 containing 5-substituted-1,3,4-thiadiazole residue were synthesized and screened in vitro for their anticancer activity.

Design, synthesis and biological activity of hybrid antifungals derived from fluconazole and mebendazole.

A novel series of triazole alcohol antifungals bearing a 5-benzoylbenzimidazol-2-ylthio side chain have been designed and synthesized as hybrids of fluconazole (a typical triazole antifungal) and mebendazole (an anthelmintic agent with antifungal activity). The title compounds were synthesized via the reaction of an appropriate oxirane and desired 2-mercaptobenzimidazole. Although there was possibility for formation of different N-substituted or S-substituted products, the structures of final compounds were assigned as thioether congeners by using C NMR spectroscopy.

Synthesis of 4-Hydroxycoumarin-Based Triazoles/Oxadiazoles as Novel Anticancer Agents.

A series of novel 3-substituted-4-hydroxycoumarins 7 and 8 containing (5-aryl-1,3,4-oxadiazol-2-yl)thio or (4-amino-5-aryl-4H-1,2,4-triazol-3-yl)thio moieties have been synthesized and evaluated as anticancer agents. The in vitro MTT assay of compounds against hepatocellular carcinoma (HepG2), breast cancer (MCF7) cells, and a human colorectal adenocarcinoma cell line with epithelial morphology (HT29) indicated that the HepG2 cells had more susceptibility to the tested compounds. Indeed, all compounds (with the exception of 7b, 7c, 7g, and 8g) were more potent than the standard drug doxorubicin against HepG2 cells (IC values=1.

Evaluation of anti-parasitic activities of new quinolones containing nitrofuran moiety against Toxoplasma gondii.

Toxoplasmosis is a disease with a worldwide prevalence that is caused by Toxoplasma gondii. Pyrimethamine and sulfadiazine are two pharmacological agents commonly used to treat of this infection. However, they are accompanied by some side effects.

Application of emetine in SARS-CoV-2 treatment: regulation of p38 MAPK signaling pathway for preventing emetine-induced cardiac complications.

Emetine is one of the most highly potent anti-SARS-CoV-2 agents ever identified. In addition to having strong anti-SARS-CoV-2 activities, emetine has other valuable therapeutic effects such as strong anti-inflammatory and anti-arterial pulmonary hypertension (APH) properties, which are suitable for the treatment of COVID-19. Its proper concomitant therapeutic effect has led researchers to test this compound in clinical trials to combat COVID-19.

Papaverine, a promising therapeutic agent for the treatment of COVID-19 patients with underlying cardiovascular diseases (CVDs).

The causative agent of coronavirus disease-2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters the host cells via an angiotensin-converting enzyme 2 (ACE2)-mediated endocytosis-dependent manner. Because ACE2 is highly expressed in the heart, SARS-CoV-2 can severely infect heart tissue and arteries, causing acute and chronic damage to the cardiovascular system. Therefore, special attention should be paid to finding appropriate agents to protect this vital system during COVID-19 treatment.

Application of kojic acid scaffold in the design of non-tyrosinase enzyme inhibitors.

Kojic acid (KA) is a hydroxypyranone natural metabolite mainly known as tyrosinase inhibitor. Currently, this compound is used as a whitening agent in cosmetics and as an anti-browning agent in food industry. Given the easy-manipulation in different positions of the KA molecule, many investigations have been carried out to find new tyrosinase inhibitors derived from KA.

Recent applications of vinyl sulfone motif in drug design and discovery.

Vinyl sulfone with electrophilic character is not only a versatile building block for various organic transformations but also is a key structural unit in a large number of biologically active molecules. In the recent decades vinyl sulfone has attracted much attention due to its potential as a privileged structural motif in medicinal chemistry for the drug discovery and development. It can be found in the chemical structure of many leads and drug candidates such as Rigosertib, Recilisib, K11777, WRR-483 and BAY 11-7085.

Synthetic approaches and structural diversity of triazolylbutanols derived from voriconazole in the antifungal drug development.

Voriconazole (VCZ) was the first approved triazole antifungal drug with 1-(1H-1,2,4-triazol-1-yl)butan-2-ol substructure. This drug showed a broad spectrum of activity, especially against yeasts and molds, and opened a new avenue toward the novel class of systemic antifungal agents. Modification of 2-fluoropyrimidine in the side chain of VCZ resulted in a newer generation of triazolylbutanols including efinaconazole, albaconazole, ravuconazole, and isavuconazole with the favorable antifungal spectrum, enhanced pharmacokinetic properties, and tolerable toxicity profiles.

Therapeutic potential of quinazoline derivatives for Alzheimer's disease: A comprehensive review.

Quinazolines are considered as a promising class of bioactive heterocyclic compounds with broad properties. Particularly, the quinazoline scaffold has an impressive role in the design and synthesis of new CNS-active drugs. The drug-like properties and pharmacological characteristics of quinazoline could lead to different drugs with various targets.

Design, synthesis and biological evaluation of naphthalene-derived (arylalkyl)azoles containing heterocyclic linkers as new anticonvulsants: A comprehensive in silico, in vitro, and in vivo study.

In continuation of our research to find strong and safe anticonvulsant agents, a number of (arylalkyl)azoles (AAAs) containing naphthylthiazole and naphthyloxazole scaffolds were designed and synthesized. The in vivo anticonvulsant evaluations in BALB/c mice revealed that some of them had significant anticonvulsant activity in both maximal electroshock (MES) and pentylenetetrazole (PTZ) models of epilepsy. The best profile of activity was observed with compounds containing imidazole and triazole rings (C1, C6, G1, and G6).

Current development of sigma-2 receptor radioligands as potential tumor imaging agents.

Sigma receptors are transmembrane proteins with two different subtypes: σ and σ. Because of its overexpression in tumors, the σ receptor (σR) is a well-known biomarker for cancer cells. A large number of small-molecule ligands for the σRs have been identified and tested for imaging the proliferative status of tumors using single photon emission computed tomography (SPECT) and positron emission tomography (PET).

A review on the structures and biological activities of anti-Helicobacter pylori agents.

Helicobacter pylori is one of the main causal risk factor in the generation of chronic gastritis, gastroduodenal ulcers and gastric carcinoma. Thus, the eradication of H. pylori infection is an important way for preventing and managing the gastric diseases.

Synthesis and Biological Evaluation of Tc-Labeled Phenylpiperazine Derivatives as Selective Serotonin-7 Receptor Ligands for Brain Tumor Imaging.

With a poor prognosis, glioblastoma multiforme is the most aggressive tumor of the central nervous system in humans. The aim of this study was to develop novel tracers for the tumor targeting and imaging of overexpressed serotonin-7 receptors (5-HTRs) in U-87 MG glioma xenografted nude mice. Two phenylpiperazine derivatives named as and were designed, and the corresponding radiotracers Tc- and Tc- were synthesized in high radiochemical purity (>95%).

Synthesis, in silico, in vitro and in vivo evaluations of isatin aroylhydrazones as highly potent anticonvulsant agents.

In this study, a series of new isatin aroylhydrazones (5a-e and 6a-e) was synthesized and evaluated for their anticonvulsant activities. The (Z)-configuration of compounds was confirmed by H NMR. In vivo studies using maximal electroshock (MES) and pentylenetetrazole (PTZ) models of epilepsy in mice revealed that while most of compounds had no effect on chemically-induced seizures at the higher dose of 100 mg/kg but showed significant protection against electrically-induced seizures at the lower dose of 5 mg/kg.

Synthesis and biological assessment of ciprofloxacin-derived 1,3,4-thiadiazoles as anticancer agents.

The quinolone-3-carboxylic acid scaffold is essential structure for antibacterial activity of fluoroquinolones such as ciprofloxacin. Modification of 3-carboxylic functionality in this structure can be used for switching its activity from antibacterial to anticancer. Accordingly, a series of C-3 modified ciprofloxacin derivatives containing N-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-carboxamide moiety was synthesized as novel anticancer agents.

Data on molecular docking of tautomers and enantiomers of ATTAF-1 and ATTAF-2 selectivty to the human/fungal lanosterol-14α-demethylase.

The data have been obtained for tautomers and enantiomers of ATTAF-1 and ATTAF-2 that were developed based on antifungal standard drugs with triazole scaffold. These compounds were docked into the human and fungal lanosterol-14α-demethylase. In order to validate the data, 8 standard triazole antifungal drugs (Fluconazole, Itraconazole, Posaconazole, Ravuconazole, Albaconazole, Voriconazole, Isavuconazole and Efinaconazole) were also docked into the human and fungal lanosterol-14α-demethylase.

Kojic acid-natural product conjugates as mushroom tyrosinase inhibitors.

As part of our effort to develop potential tyrosinase inhibitors, we have conjugated the well-known tyrosinase inhibitor kojic acid (KA) with several phenolic natural products such as umbelliferone, sesamol, thymol, carvacrol, eugenol, isoeugenol, vanillin, isovanillin, and apocynin that some reports have shown their activity on tyrosinase enzyme. The designed compounds were synthesized using click reaction and 1,2,3-triazole formation. All compound showed potent anti-tyrosinase activity significantly higher than KA.