Band 79, Heft 9-10

Theranostics refers to the combination of diagnostic biomarkers with therapeutic agents that share a specific target expressed by diseased cells and tissues. Nuclear medicine is an exciting component explored for its applicability in theranostic concepts in clinical and research investigations. Nuclear theranostics is based on the employment of radioactive compounds delivering ionizing radiation to diagnose and manage certain diseases employing binding with specifically expressed targets. In the realm of personalized medicine, nuclear theranostics stands as a beacon of potential, potentially revolutionizing disease management. Studies exploring the theranostic profile of radioactive compounds have been presented in this review along with a detailed explanation of radioactive compounds and their theranostic applicability in several diseases. It furnishes insights into their applicability across diverse diseases, elucidating the intricate interplay between these compounds and disease pathologies. Light is shed on the important milestones of nuclear theranostics beginning with radioiodine therapy in thyroid carcinomas, MIBG labelled with iodine in neuroblastoma, and several others. Our perspectives have been put forth regarding the most important theranostic agents along with emerging trends and prospects.

In this present study, new chalcone derivatives were synthesized from 4-aminoacetophenone, which were confirmed by spectroscopic methods. The toxic risks of chalcones to humans and the environment were investigated by a web-based platform called ADMETlab. With this program, the possible toxic effects of the compounds on liver, respiratory system, and eyes were evaluated. For the topical insecticidal activity, adult female Caribbean fruit fly, Anastrepha suspensa , was targeted. Results of the toxicity tests showed that chalcone derivatives are effective against female A. suspensa . Among the synthesized chalcones, 1-(4-cinnamoylphenyl)-3-( p -tolyl)urea ( 2 ) exhibited the greatest insecticidal activity, resulting in 73 % mortality at 100 µg/fly after 24 h, whereas other derivatives showed less than 30 % mortality. Our results demonstrate that insecticidal activity may be modulated by the presence of a certain phenyl ring in the structure of derivative 2 and, therefore, has potential for design of efficient chemicals for tephritid fruit fly management.

Cymbopogon proximus comprises several phytoconstituent classes that are reported to possess anticancer activity; however, studies on the anticancer potentials of the plant are lacking. C. proximus was extracted using solvents with increasing polarity. In-vitro cytotoxic activity of C. proximus extracts was examined against liver (HepG2), lung (A549), prostate (PC3), and bone (MG63) cell lines using MTT assay in comparison to doxorubicin. Flow cytometry was used to analyze the cell cycle for identification of the phase of inhibition. Chemical composition of the most active fraction was examined using the GC/MS technique. Molecular docking was used to explore the mechanism of cytotoxicity against A549, and the results were confirmed by Western blot analysis. Petroleum ether fraction was the highly effective fraction against A549 with IC 50  = 14.02 ± 2.79. GC/MS analysis of Pet.Eth led to the identification of nine compounds in unsaponifiable matter and 27 components in the saponifiable fraction. Di-N-octyl phthalate, 3-β-hydroxylean-11.13(18)-dien-30-oic acid methyl ester, elemol hydrocarbons, linoelaidic acid and linoleic acid demonstrated the lowest docking binding scores and similar binding modes against CDK2 as compared to that attained by the native ligand R-Roscovitine “CDK2 ATP inhibitor”. Western blot analysis demonstrated that CDK2/cyclinA2 protein expression has been suppressed in A549 cell lines by Pet.Eth fraction.

Nine compounds were isolated and identified from ethanolic extracts of Saposhnikovia divaricata , including one new alkaloid ( 1 ), one new pentacyclic triterpenoid ( 9 ), and seven known alkaloids ( 2 – 8 ). Structural elucidation of compounds 1 and 9 was established by 1D and 2D NMR spectra referring to the literature, together with high-resolution mass spectrometric analysis. All compounds were evaluated for antiproliferative activity against two cancer cell lines (LN229, A549) in vitro . Compounds ( 1 – 9 ) showed no significant antiproliferative activity.

Cancer remains a significant health challenge globally, requiring the development of targeted chemotherapeutics capable of specifically inhibiting cancer cell growth. Angiogenesis is one of the key features of tumor growth and metastasis and is, therefore, an important target for the treatment of many tumors. The vascular endothelial growth factor (VEGF) signaling pathway has proven to be a promising lead in anticancer therapy due to the central role it plays in tumor angiogenesis. Vascular endothelial growth factor receptor-2 (VEGFR-2) is a key mediator in the signaling pathway regulating angiogenesis. Targeting VEGFR-2 may disrupt angiogenesis, leading to a reduction in tumor blood supply and tumor progression. The design, synthesis, and assessment of novel VEGFR-2 inhibitor derivatives are the focus of this study, with particular emphasis on incorporating the pyrazole–thiadiazol pharmacophore into the molecular structure. Taking advantage of the pharmacophoric properties of pyrazole and 1,3,4-thiadiazol, compounds with different substituents in the main structure were designed and synthesized. The compounds were also evaluated for antiproliferative activity against cancer cell lines. Compound 4e demonstrated the highest activity among all compounds, with an IC 50 of 9.673 ± 0.399 μM against HT-29 cells and 23.081 ± 0.400 μM against NIH3T3 cells. To further support the inhibitory activity of compound 4e , an in silico study was performed. Compound 4e demonstrated strong binding to the active site of VEGFR-2 in molecular docking studies, forming hydrogen bonds with key amino acid residues. The stability of the compound in the enzyme’s active site was demonstrated through molecular dynamics simulations.

Tephrosia vogelii is a traditional medicinal plant used to treat hypertension, diarrhea and urinary disorders. Silica gel chromatographic separation of CH 2 Cl 2 /MeOH (1:1) roots extract of T. vogelii afforded seven compounds namely; β-sitosterol ( 1a ), stigmasterol ( 1b ), 6a, 12a-dehydro-deguelin ( 2 ), tephrosin ( 3 ), maackiain ( 4 ), obovatin ( 5 ) and 6-oxo, 6a, 12a-dehydro-deguelin ( 6 ). GC-MS analysis of essential oils from the root of T. vogelii displayed a total of 17 compounds of which cis-nerolidol (41.7 %) and cadinol (19.7 %) were the major constituents. CH 2 Cl 2 /MeOH (1:1) extract, MeOH extract, maackiain ( 4 ) and obovatin ( 5 ) showed moderate inhibitory activity against Pseudomonas aeruginosa with MIC value of 0.5, 0.66, 0.83 and 0.83 mg/mL, respectively, compared to ciprofloxacin (MIC of 0.078 μg/mL). 6a, 12a-dihydro-deguelin ( 2 ), and 6-oxo, 6a, 12a-dehydro-deguelin ( 6 ) displayed significant activity against S. epidermis with MIC values of 0.66 mg/mL. Tephrosin ( 3 ) and maackiain ( 4 ) also showed moderate antibacterial activity against Staphylococcus aureus and Proteus mirabilis with MIC values of 0.83 and 0.5 mg/mL, respectively, compared to ciprofloxacin (0.312 μg/mL). The radical scavenging activity results indicated that tephrosin ( 3 ), obovatin ( 5 ) and 6-oxo, 6a, 12a-dehydro-deguelin ( 6 ) showed potent DPPH scavenging activity with IC 50 values of 10.97, 10.43 and 10.73 μg/mL, respectively, compared to ascorbic acid (IC 50 of 5.83 μg/mL). The docking prediction results revealed that 6a, 12a-dehydro-deguelin ( 2 ) displayed the best binding energy of −8.1 kcal/mol towards pyruvate kinase of S. aureus (PDB ID: 3T07) and −7.9 kcal/mol towards P. mirabilis urease (PDB ID: 1E9Y) and DNA gyrase B of Escherichia coli (PDB: 4F86) receptors compared to ciprofloxacin (−7.2 to −8.0 kcal/mol). Maackiain ( 4 ) and obovatin ( 5 ) displayed the minimum binding energy of −7.9 and −8.2 kcal/mol towards the LasR protein of P. aeruginosa (PDB: ID 2UV) and S. epidermidis FtsZ (PDB: ID 4M8I), respectively. The SwissADME drug-likeness and Pro Tox II toxicity prediction results indicated that compounds ( 2 – 6 ) obeyed Lipinski’s rule of five with 0 violations and none of them were found to be hepatotoxic, mutagenic, and cytotoxic, respectively. The in vitro assessment results supported by the in silico analysis revealed that crude extracts and isolated compounds showed promising antibacterial and antioxidant activity, which proves the therapeutic potential of the roots of T. vogelii .

Anaxagorea luzonensis A. Gray, a member of the Annonaceae family, has been used to treat a variety of illnesses for a long time. For the first time, A . luzonensis volatile compounds (ALVCs) were extracted from the leaves, and the components were identified using gas chromatography-mass spectrometry (GC-MS). Further, the main compositions of ALVCs were also assessed for their ability to bind with anti-inflammatory proteins using a docking model. In addition, in vitro tests e.g. inhibition of protein degradation and the inhibition of nitric oxide release using RAW264.7 macrophage cells were utilized for evaluating the anti-inflammatory activity. The results showed that the principal compounds of ALVCs were bulnesol (34.1 %), cubitene (17.8 %), β -eudesmol (10.4 %), epi -longipinanol (5.9 %), and ( Z )-nerolidyl acetate (5.5 %). Three compounds viz. bulnesol, cubitene, and β -eudesmol bound firmly to cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), as shown by the in silico analysis, similar to the positive control diclofenac. ALVCs effectively inhibited protein degradation with the IC 50 of 31 ± 2.3 μg/mL and inhibited nitric oxide production with the IC 50 of 43.30 ± 3.37 μg/mL. These findings showed that ALVCs might have a promising anti-inflammatory effect by blocking several inflammatory proteins.