Recent Developments in the Synthesis of Benzothiazoles and their Anti-cancer Mechanistic Discoveries.

Benzothiazole derivatives have garnered considerable attention owing to their versatile chemical scaffold and remarkable biological activities. The article provides an in-depth analysis of the diverse structural modifications and strategies employed to enhance the anticancer potential of these compounds from the period of 2020 to 2024. It discusses the role of structure-activity relationships (SAR) and computational approaches in optimizing benzothiazole derivatives for selective and effective cancer treatment.

Tc-labeled benzenesulfonamide derivative-entrapped gold citrate nanoparticles as an auspicious tumour targeting.

Sulfonamide derivatives are a significant class of medicinal compounds. Gold nanoparticles (AuNPs) offer precise cancer treatment through targeted delivery, boasting high drug-loading capacity and low toxicity. This study aimed to develop and evaluate 99mTc-labeled benzenesulfonamide derivative-entrapped gold citrate nanoparticles as a tumor-targeting agent.

Synthesis of S-alkylated oxadiazole bearing imidazo[2,1-b]thiazole derivatives targeting breast cancer: In vitro cytotoxic evaluation and in vivo radioactive tracing studies.

Breast cancer is the most common invasive cancer diagnosed in women, accounting for most cancer-related fatalities globally. Numerous investigations have revealed that breast cancer is characterized by abnormal expression and maintenance of EGFR levels. In terms of structural study and optimization of several EGFR inhibitors, two series of oxadiazole bearing imidazo[2,1-b]thiazole derivatives were designed and synthesized as potential EGFR inhibitors and assessed for their antitumor activity at NCI-USA.

pH-Sensitive doxorubicin delivery using zinc oxide nanoparticles as a rectified theranostic platform: anti-proliferative, apoptotic, cell cycle arrest and radio-distribution studies.

Despite enormous advancements in its management, cancer is the world's primary cause of mortality. Therefore, tremendous strides were made to produce intelligent theranostics with mitigated side effects and improved specificity and efficiency. Thus, we developed a pH-sensitive theranostic platform composed of dextran immobilized zinc oxide nanoparticles, loaded with doxorubicin and radiolabeled with the technetium-99m radionuclide (Tc-labelled DOX-loaded ZnO@dextran).

Multi-functionalization of reduced graphene oxide nanosheets for tumor theragnosis: Synthesis, characterization, enzyme assay, in-silico study, radiolabeling and in vivo targeting evaluation.

Background: In this study, a combination of nanotechnology, organic synthesis and radiochemistry were utilized in order to design an efficient nano-system conjugated with a suitable radionuclide and an antitumor agent for possible application as tumor theragnostic agent.

Method: Four novel compounds (3 and 4a-c) bearing tetrahydroquinazoline-7-sulfonohydrazide or 1,2,3,4-tetrahydroquinazoline-7-sulfonamide scaffold were designed. Then, docking study predicted that the compounds can be considered as potential inhibitors for PARP-1.

Highlight selection of radiochemistry and radiopharmacy developments by editorial board.

Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development.

Main Body: This selection of highlights provides commentary on 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals.

Conclusion: Trends in radiochemistry and radiopharmacy are highlighted.

The Development and Validation of Radiopharmaceuticals Targeting Bacterial Infection.

The International Atomic Energy Agency organized a technical meeting at its headquarters in Vienna, Austria, in 2022 that included 17 experts representing 12 countries, whose research spanned the development and use of radiolabeled agents for imaging infection. The meeting focused largely on bacterial pathogens. The group discussed and evaluated the advantages and disadvantages of several radiopharmaceuticals, as well as the science driving various imaging approaches.

Computational, in vitro and radiation-based in vivo studies on acetamide quinazolinone derivatives as new proposed purine nucleoside phosphorylase inhibitors for breast cancer.

The present work describes a quinazolinone-based lead optimization for the development of novel purine nucleoside phosphorylase (PNP) inhibitors with quinazolinone scaffold. Nineteen compounds were proposed and docked against PNP, the best 14 compounds with highest docking and affinity scores and low RMSD values were synthesized. Synthesis of new quinazolinone derivatives with variable acetamide substituents on two positions on quinazoline ring was performed.

New 5-Aryl-1,3,4-Thiadiazole-Based Anticancer Agents: Design, Synthesis, In Vitro Biological Evaluation and In Vivo Radioactive Tracing Studies.

A new series of 5-(4-chlorophenyl)-1,3,4-thiadiazole-based compounds featuring pyridinium (), substituted piperazines (), benzyl piperidine (), and aryl aminothiazoles () heterocycles were synthesized. Evaluation of the cytotoxicity potential of the new compounds against MCF-7 and HepG2 cancer cell lines indicated that compounds and displayed the highest activity toward the tested cancer cells. A selectivity study demonstrated the high selective cytotoxicity of and towards cancerous cells over normal mammalian Vero cells.

IAEA Contribution to Nanosized Targeted Radiopharmaceuticals for Drug Delivery.

The rapidly growing interest in the application of nanoscience in the future design of radiopharmaceuticals and the development of nanosized radiopharmaceuticals in the late 2000's, resulted in the creation of a Coordinated Research Project (CRP) by the International Atomic Energy Agency (IAEA) in 2014. This CRP entitled ' involved a team of expert scientist from various member states. This team of scientists worked on a number of cutting-edge areas of nanoscience with a focus on developing well-defined, highly effective and site-specific delivery systems of radiopharmaceuticals.

New frontier radioiodinated probe based on in silico resveratrol repositioning for microtubules dynamic targeting.

Purpose: As the '' drug discovery faces a highly attrition rates, drug repositioning procures a heighten concern in identifying novel uses for existing medications. This study aimed to fabricate radioiodinated resveratrol as a potent microtubules interfering agent for cancer theragnosis.

Methods: Resveratrol was radiolabeled with radioactive iodine where the radioiodination efficiency was enlightened and the computational approaches were employed to investigate the affinity and specificity with tubulins.

New quinoxaline compounds as DPP-4 inhibitors and hypoglycemics: design, synthesis, computational and bio-distribution studies.

The current work represents the design and synthetic approaches of a new set of compounds 6-10 bearing the 1,4-dimethyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide scaffold. The biological evaluation revealed that most of the new compounds were promising selective dipeptidyl peptidase-IV (DPP-4) inhibitors and hypoglycemic agents utilizing linagliptin as a standard drug. The acute toxicity examination confirmed the safety profile of all compounds.

Multifunctional Tc-5-azacitidine Gold Nanoparticles: Formulation, Cytotoxicity, Radiosynthesis, and Pharmacokinetic Study.

Background: 5-azacitidine is a very potent chemotherapeutic agent that suffers from certain disadvantages.

Objective: This study aims to prepare gold nanoparticles as a new nano-formula of 5-azacitidine that can improve its bioavailability and decrease its side effects.

Methods: 5-azacytidine-loaded GA-AuNPs were prepared and characterized by UV-Vis spectroscopy, infrared (IR), and electronic transmission microscope (TEM).

Hepatoprotective, antioxidant and anti-inflammatory potentials of Vit-E/C@SeNPs in rats: Synthesis, characterization, biochemical, radio-biodistribution, molecular and histopathological studies.

This study aimed to synthesize a nano-structure between selenium, Vit. C, and Vit. E (Vit-E/C@SeNPs) as a promising protective and therapeutic agent for hepatocellular carcinoma.

Polyethylene oxide-polyacrylic acid-folic acid (PEO-PAAc) nanogel as a Tc targeting receptor for cancer diagnostic imaging.

Nanoparticles are frequently used as targeting delivery systems for therapeutic and diagnostic radiopharmaceuticals. Polyethylene oxide-polyacrylic acid (PEO-PAAc) nanogel was prepared via γ-radiation-induced polymerization. Variable factors affecting nanoparticles size were investigated.

Amelioration of Tumor Targeting and In Vivo Biodistribution of Tc-Methotrexate-Gold Nanoparticles (Tc-Mex-AuNPs).

Gold nanoparticles (AuNPs) represent very attractive and promising drug delivery carriers due to their unique dimensions, adjustable surface functions, and controllable drug release. Therefore, AuNPs are used to overcome the limitations of conventional chemotherapy, for example methotrexate (Mex), one of the first-generation chemotherapy drugs for cancer treatment, whose usefulness has been restricted due to drug resistance and dose-dependent side effects. In the present study, the AuNPs drug delivery system was synthesized and loaded with technetium-99 m radiolabeled Methotrexate (Tc-Mex) to produce new potential nanoradiopharmaceutical for tumor targeting and further imaging.

Novel thiobarbiturates as potent urease inhibitors with potential antibacterial activity: Design, synthesis, radiolabeling and biodistribution study.

Urease enzyme is a virulence factor that helps in colonization and maintenance of highly pathogenic bacteria in human. Hence, the inhibition of urease enzymes is well-established to be a promising approach for preventing deleterious effects of ureolytic bacterial infections. In this work, novel thiobarbiturate derivatives were synthesized and evaluated for their urease inhibitory activity.

Tc-gallic-gold nanoparticles as a new imaging platform for tumor targeting.

Early and accurate detection of tumor assists in identifying more effective therapies. Gold nanoparticles (GNPs) were synthesized by green synthesis method using gallic acid (GA) then characterized and labeled with technetium-99m. This new platform was biologically evaluated in both normal and solid tumor bearing mice.

Tc-doxorubicin-loaded gallic acid-gold nanoparticles (Tc-DOX-loaded GA-Au NPs) as a multifunctional theranostic agent.

The development of cancer theranostic nanomedicines is recommended to concurrently achieve and evaluate the therapeutic benefit and progress. The current work aims to develop gallic acid-gold nanoparticles (GA-Au NPs) as a theranostic probe for Tc-Doxorubicin (Tc-DOX) based on the spatiotemporal release pattern induced intra-tumoral (IT) delivery. DOX-loaded GA-Au NPs were developed and identified via UV-Vis spectroscopy.

Exhibiting the diagnostic face of selenium nanoparticles as a radio-platform for tumor imaging.

Selenium nanoparticles (SeNPs) have become one of the most prospective and promising tools in the course of cancer diagnosis and therapy. Here we describe the synthesis of a novel radioactive platform for tumor imaging using selenium nanoparticles. SeNPs were synthetized using dithionite and glutathione as reducing and capping agent respectively with 5 mmol/L sodium selenite as a precursor and then SeNPs radiolabeled with technetium-99 m, the most common and famous radioactive isotope used for imaging purposes.

New acrylamide-sulfisoxazole conjugates as dihydropteroate synthase inhibitors.

New functionalized acrylamide derivatives bearing sulfisoxazole moiety were designed to target bacterial dihydropteroate synthase (DHPS). The in vitro antimicrobial activities of these compounds were assessed. The E-configuration of compound 5b was proved by single crystal X-ray analysis.

New benzenesulfonamide scaffold-based cytotoxic agents: Design, synthesis, cell viability, apoptotic activity and radioactive tracing studies.

A new series of thiazolidinone (5a-g), thiazinone (9a-g) and dithiazepinone (9a-g) heterocycles bearing a benzenesulfonamide scaffold was synthesized. Cytotoxicity of these derivatives was assessed against MCF-7, HepG2, HCT-116 and A549 cancer cell lines and activity was compared to the known cytotoxic agents doxorubicin and 5-FU where the most active compounds displayed better to nearly similar IC values to the reference compounds. For assessing selectivity, the most active derivatives against MCF-7, 5b, 5c and 5e, were also assessed against the normal breast cell line MCF-10 A where they demonstrated high selective cytotoxicity to cancerous cells over that to normal cells.

Rational design of some substituted phenyl azanediyl (bis) methylene phosphonic acid derivatives as potential anticancer agents and imaging probes: Computational inputs, chemical synthesis, radiolabeling, biodistribution and gamma scintigraphy.

Bisphosphonates are widely used for treatment of osteoporosis. Recently, they have been reported to be effective anticancer agents. In this work, we designed some substituted phenyl (azanediyl) bis (methylene phosphonic acid) to be tested for their anticancer effect.

Superiority of DEAE-Dx-Stabilized Cationic Bile-Based Vesicles over Conventional Vesicles for Enhanced Hepatic Delivery of Daclatasvir.

The purpose of our study was to improve the delivery of a direct-acting antiviral drug, daclatasvir, to the site of action, liver tissues, using physically and biologically stable cationic bile-based vesicles. Accordingly, cationic bile-based vesicles were prepared as pro-bile-based vesicles and diethylaminoethyl dextran (DEAE-Dx)-stabilized bile-based vesicles to increase their stability without negatively affecting their hepatic affinity. The prepared bile-based vesicles were characterized for particle size, polydispersity index, ζ-potential, in vitro daclatasvir release, and ex vivo permeation using non-everted gut sac intestine.

Adaptation of hard gelatin capsules for oral delivery of aqueous radiopharmaceuticals.

Purpose: Oral administration of Iodine (I) solutions causes high risk of contamination for patients and dispensers. The objective of the study was to adapt hard gelatin capsules (HGCs) for filling with radiopharmaceutical solutions without deformation.

Methods: Polystyrene (PS) internally lining films with different thicknesses were used to protect HGCs.