Potential Agents Research Articles

Sequentially Activated Smart DNA Nanospheres for Photoimmunotherapy and Immune Checkpoint Blockade.

Due to the inherent immunosuppression and immune evasion of cancer cells, combining photoimmunotherapy with immune checkpoint blockade leverages phototherapy and immune enhancement, overcoming mutual limitations and demonstrating significant anticancer potential. The main challenges include nonspecific accumulation of agents, uncontrolled activation, and drug carrier safety. Smart DNA nanospheres (NS) is developed with targeted delivery and controllable release of photosensitizers and immune agents to achieve effective synergistic therapy and minimize side effects. The multifunctional NS incorporate a targeting module for programming aptamers, a response module for programming i-motif and DNA/RNA hybrid sequences, and a therapeutic module for packaging photosensitizers and PD-L1 siRNA. NS navigate to the tumor site and are sequentially activated by intracellular acid and enzymes to release photosensitizers and programmed death ligand 1 (PD-L1) small interfering RNA (siRNA) programmed death protein 1 (PD-1) and programmed cell death ligands. Besides tumor killing and immune promotion, activated NS downregulate PD-L1 expression, alleviating immune tolerance and evasion, thus enhancing the immune response. These results indicate that NS significantly enhance antitumor immune responses, synergistically improve antitumor efficacy, and reduce systemic toxicity. This study broadens the application of DNA nanomaterials in precision drug delivery and tumor therapy.

Low-Dose Ozone as a Eustress Inducer: Experimental Evidence of the Molecular Mechanisms Accounting for Its Therapeutic Action

Ozone (O3) is an unstable, highly oxidative gas that rapidly decomposes into oxygen. The therapeutic use of O3 dates back to the beginning of 20th century and is currently based on the application of low doses, inducing moderate oxidative stress that stimulates the antioxidant cellular defences without causing cell damage. In recent decades, experimental investigations allowed the establishment of some basic mechanisms accounting for the therapeutic effects of eustress-inducing low-dose O3. In this review, special attention was given to the impact of O3 administration on the cell oxidant–antioxidant status, O3 anti-inflammatory and analgesic properties, efficacy in improving tissue regeneration, and potential anticancer action. Low O3 concentrations proved to drive the cell antioxidant response mainly by activating nuclear factor erythroid 2-related factor 2. The anti-inflammatory effect relies on the downregulation of pro-inflammatory factors and the modulation of cytokine secretion. The painkilling action is related to anti-inflammatory processes, inhibition of apoptosis and autophagy, and modulation of pain receptors. The regenerative potential depends on antioxidant, anti-inflammatory, anti-apoptotic, and pro-proliferative capabilities, as well as fibroblast activation. Finally, the anticancer potential is based on oxidant and anti-inflammatory properties, as well as the inhibition of cell proliferation, invasion, and migration and the induction of apoptosis.

Isolation and biomimetic synthesis of acylphloroglucinol meroterpenoids as anti-breast cancer agents from Dryopteris crassirhizoma.

Two new acylphloroglucinol-nerolidol meroterpenoids (APNMs) [(±)-1 and (±)-2], with a skeleton of mixed sesquiterpene and dimeric acylphloroglucinol biosynthetic origin, were isolated from the medicinal pteridophyte Dryopteris crassirhizoma. Inspired by the proposed biosynthetic pathway, we initially completed the biomimetic syntheses of eight optically active Dryopteris APNMs (1-8) in a one-pot domino reaction. The structures of APNMs 1-8 including their absolute configurations were unambiguously established by a combination of NMR analysis, ECD calculations, and synthetic methods. Furthermore, an underlying method based on NMR data to assign the stereochemistry of the long-chain alcohol moieties in APNMs was revealed. Anti-triple negative breast cancer (anti-TNBC), antifungal and antibacterial activities of the synthetic meroterpenoids were evaluated. All tested compounds exhibited cytotoxicity against TNBC cells MDA-MB-231 with IC50 values in the range of 1.22-27.43 μM, with (-)-8 being the most potent antitumor agent (IC50: 0.48 μM; selectivity index: 32.04). This study resulted in the biomimetic synthesis of APNMs for the first time and positioned APNMs from D. crassirhizoma as a new class of promising candidates for the development of new anti-TNBC drugs.

Synthesis, characterization and evaluation of in-vitro anticancer potential of novel fluorinated 5-Benzylidene-3-ethyl-2-(2-methyl-3-trifluoromethyl-phenylimino)-thiazolidin-4-one derivatives

Synthesis, characterization and evaluation of in-vitro anticancer potential of novel fluorinated 5-Benzylidene-3-ethyl-2-(2-methyl-3-trifluoromethyl-phenylimino)-thiazolidin-4-one derivatives

Vibrational spectroscopic characterization, quantum chemical, molecular docking and molecular dynamics investigations of cyclo(L-phenylalanyl-L-proline), an anticancer agent

The molecular structure and spectral properties of cyclo(L-Phenylalanyl-L-Proline) dipeptide, which has several biological activities, were investigated. Firstly, conformational preference of the cyclo(L-Phenylalanyl-L-Proline) was searched and obtained lowest energy conformer of the cyclic dipeptide was then optimized using Density Functional Theory with wb97xd/6-311++G(d,p) level of theory. A detailed vibrational spectral analysis has been carried out and assignments of the fundamental modes have been proposed. The experimental vibrational wavenumbers of the investigated compound display good agreement with the computed values. The Frontier Molecular Orbitals, Molecular Electrostatic Potential and electronic transitions of the investigated compound were discussed. In addition, the 1H and 13C NMR chemical shifts of the cyclic dipeptide were calculated and the results were compared with the experimental values. Also, to evaluate the anticancer potential, molecular docking studies of cyclo(L-Phenylalanyl-L-Proline) within the ATP-binding sites of both wild type (EGFRWT; ID: 4HJO) and mutant (EGFRT790M; ID: 3W2O) Epidermal Growth Factor Receptor were performed. The results indicated that cyclo(Phe-Pro) has high binding affinities toward both EGFRWT (−6.6 kcal/mol) and EGFRT790M (−7.7 kcal/mol) receptors, thus, has good anticancer activity and also has potential to overcome drug resistance in therapy. Molecular dynamics simulations on cyclo(L-Phenylalanyl-L-Proline)-wild type complex were conducted through a 50-nanosecond timed to investigate the ligand-receptor interactions in more detail, and to determine the binding free energy accurately. The binding free energy of the cyclo(L-Phenylalanyl-L-Proline)-wild type complex was calculated to be −27.18 kcal/mol.

Acute severe ulcerative colitis: using JAK-STAT inhibitors for improved clinical outcomes

Acute Severe Ulcerative Colitis (ASUC) is a well-known and potentially fatal disease state, characterized by symptoms of systemic toxicity including fever, severe anemia, elevated inflammatory markers, and autonomic instability. The life-threatening nature of this condition requires clinicians to make prompt diagnoses and take rapid action, either directing patients towards surgical interventions or medical management. Failure to treat ASUC may lead to toxic dilation of the colon, hemorrhage, or sepsis. Current algorithms suggest the use of intravenous (IV) corticosteroids upon diagnosis, with transition to oral corticosteroids, calcineurin inhibitors or tumor necrosis factor (TNF) inhibitors upon reduction of severe symptoms for candidates deemed to be amenable to medical management. Within these classes, TNF inhibitors such as Infliximab (IFX) have proven to be the most safe, efficacious, and tolerable for patients. While IFX has much data supporting its benefits in achieving short term remission, there are still high rates of long-term need for colectomy and failure to maintain remission. This is due to interactions between the inflamed gastrointestinal tract, the increased metabolic activity seen in ASUC, and intrinsic pharmacodynamic properties of IFX. Certain novel studies suggest that Janus Kinase (JAK-STAT) inhibitors such as Tofacitinib and Upadacitinib are potent agents to salvage clinical remission achieved by IFX, upon its failure. Here we discuss methods to optimize the dosing of IFX to maximize its efficacy, while exploring recent work done on the safety and efficacy of JAK-STAT inhibitors as a salvage therapy, therefore suggesting a novel treatment algorithm to improve clinical outcomes in medically managed ASUC patients.

Biological Evaluation of a Rhodium(III) Bipyridylsulfonamide Complex: Effects on Mitochondrial Dynamics and Cytoskeletal Remodeling in Breast Cancer Cells.

Rhodium(III) complexes have gained attention for their anticancer potential. In this study, we investigated a rhodium(III) bipyridylsulfonamide complex (2) and its ligand (L) for their effects on breast cancer (SKBr3) and noncancerous mammary cells (HB2). Both compounds significantly reduced oxidative phosphorylation (OXPHOS) and mitochondrial function in SKBr3 cells while sparing HB2 cells. Compound 2 also increased glycolysis in both lines, suggesting a metabolic shift. Mitochondrial size and shape were altered, particularly in SKBr3 cells. Additionally, both compounds reduced cancer cell migration by disrupting actin cytoskeleton organization and the Rac1/VASP signaling pathway. These findings suggest that the rhodium(III) bipyridylsulfonamide complex selectively impairs mitochondrial dynamics and cell migration in cancer cells while sparing healthy cells, providing insight into its mechanism of action and toward its use as targeted anticancer therapy. This study lays the groundwork for future in vivo studies and further optimization of these metal-based therapeutics for clinical applications.

Cytotoxic Potential of Simarouba glauca Leaf Extracts on PA1 Human Ovarian Cancer Cell Lines

ABSTRACT The phytochemical composition, anti-oxidant and cytotoxic potential of Simarouba glauca leaf extracts were examined. The anti-oxidant activity was determined by DPPH, PM and FRAP assays. The determination of cell viability was performed by MTT assay. The acetone and methanol extracts showed higher anti-oxidant capacities than other extracts. The methanol and acetone extracts inhibited PA1 ovarian cancer cell growth in a dose-dependent manner with IC50 values 106.67 ± 1.53 μg/ml−1 and 124.43 ± 3.04 μg/ml−1, respectively, compared to the standard drug Doxorubicin (IC50 = 2.91±0.03 μg/ml−1). The selectivity of the plant proved to have a promising anti-cancer potential by inhibiting PA1 ovarian cancer cell lines.

Computational and experimental insights into glycyrrhizin-loaded nanostructured lipid carriers: docking, dynamics, design optimization, and anticancer efficacy in lung cancer cells

BackgroundLung cancer (LC) remains a predominant global health concern, especially with escalating tobacco-smoking rates. Present study provides computational screening, molecular dynamics, DFT and simulation analysis of phytoconstituents on EGFR receptors (2ITY and W2O), followed by selection of highest docking score phytoconstituents among 45 for further analysis. The formulation was optimized by Central composite design. Nanostructured-lipid carriers were prepared by high-speed homogenization, combining a 1:1 ratio of liquid lipid (Castor oil) and melted solid lipid (glyceryl monostearate) with 4% surfactant (tween 80) in a water phase containing Glycyrrhizin. The resulting mixture underwent high-speed homogenization at 8000 rpm for 40 min, followed by sonication for 15 min to achieve formulation development of GNLC. The anticancer potential of GNLC have been proved by experimental analysis through MTT assay using A549 Cell lines.ResultsGlycyrrhizin was found to possess maximum docking score − 8.863 and − 8.837 on both 2ITY and W2O respectively. The study unveils Glycyrrhizin’s interactions with EGFR pivotal in cancer progression and treatment. Molecular dynamics simulations highlighted the structural and dynamic interactions within a protein–ligand complex, indicating both stability and flexibility characteristics. DFT analysis of Glycyrrhizin revealed its molecular properties, suggesting stability and potential reactivity. Glycyrrhizin loaded nanostructured lipid carriers (GNLC) have been developed and analysed by various parameters like particle size and drug release zeta potential, SEM analysis, and solubility analysis reveals critical insights into their optimization for effective drug delivery. Both GNLC and Doxorubicin (0.78–50 µg/ml) were used for the activity. The anticancer potential at 12.50, 25 and 50 µg/ml pf GNLC was found to be statistically significant and was comparable with that of standard group Doxorubicin. The observed structural transformations in Glycyrrhizin into a lipid matrix indicate potential enhancements in its drug release.ConclusionsGNLC shows promising anti-cancer potential in lung cancer, further pre-clinical and clinical studies, is crucial to validate its efficacy, safety, and integration into standard therapeutic regimens.Graphical abstract

Glucosinolate Profiles of Capparis spp. and Maerua baillonii (Capparaceae) and Cytotoxicity of Methyl Isothiocyanate-Rich Isolates from Capparis spinosa subsp. rupestris.

This study investigates the glucosinolate profiles of various Capparis spp. and Maerua baillonii, from the Capparaceae family, and evaluates the cytotoxic potential of volatile isolates from Capparis spinosa subsp. rupestris. Using UHPLC-DAD-MS/MS, GSLs were identified and quantified across different plant tissues. Glucocapparin, predominant glucosinolate in C. spinosa subsp. spinosa, C. spinosa subsp. rupestris, and M. baillonii, was isolated and analyzed by NMR in its desulfo-form. Notably, glucosinolates were absent in C. richardii and specific tissues of M. baillonii (e.g., leaves and stems), underscoring species and/or tissue-specific variability within Capparaceae. Less common glucosinolates for Capparaceae plants, such as glucocochlearin, glucohirsutin, and glucoarabin were also detected. Methyl isothiocyanate was found to be the main volatile in all isolates obtained through various isolation methods, comprising ca. 80-90% of the total volatiles. Methyl isothiocyanate-rich volatile isolates were tested for cytotoxicity against human breast cancer (MDA-MB-231) and bladder cancer (T24) cell lines using the MTT assay, showing significant activity with IC50 values of 3.81 µg/mL and 5.95 µg/mL, respectively. These findings underscore the anticancer potential of glucocapparin-bearing plants from Capparaceae family.

Nanocochleate-based delivery of quercetin with enhanced therapeutic potential: formulation, cytotoxicity and pharmacokinetics study

BackgroundQuercetin has well-proven anticancer potential through various mechanisms, but its applications in drug delivery are limited due to poor biopharmaceutical properties. The present study was aimed to formulate quercetin nanocochleates (QNC) in order to overcome these limitations. QNC formulation was fabricated by a trapping method, optimized and evaluated for various formulation aspects, in vitro cytotoxicity and pharmacokinetic parameters.ResultDeveloped nanocochleates possess particle size and encapsulation efficiency of 205.6 ± 2.55 nm and 76.36 ± 0.88%, respectively. In vitro cytotoxicity study performed using MCF-7 cell lines revealed the comparative efficiency of QNC over pure quercetin. Total growth inhibition concentration (TGI) for pure quercetin was 96.73 μg/ml, while for QNC it was 83.29 μg/ml. Pharmacokinetic study results showed improvement in Cmax and AUC after QNC formulation with increased Tmax showing sustained release.ConclusionOverall, the developed QNC formulation markedly improved cytotoxic potential and biopharmaceutical aspects.

Emissions of methane from coal fields, thermal power plants, and wetlands and their implications for atmospheric methane across the south Asian region

Abstract. Atmospheric methane (CH4) is a potent climate change agent responsible for a fraction of global warming. The present study investigated the spatiotemporal variability of atmospheric-column-averaged CH4 (XCH4) concentrations using data from the Greenhouse gases Observing SATellite (GOSAT) and the TROPOspheric Monitoring Instrument on board the Sentinel-5 Precursor (S5P/TROPOMI) from 2009 to 2022 over the south Asian region. During the study period, the long-term trends in XCH4 increased from 1700 to 1950 ppb, with an annual growth rate of 8.76 ppb yr−1. Among all natural and anthropogenic sources of CH4, the rate of increase in XCH4 was higher over the coal site at about 10.15 ± 0.55 ppb yr−1 (Paschim Bardhaman) followed by Mundra Ultra Mega Power Project at about 9.72 ± 0.41 ppb yr−1. Most of the wetlands exhibit an annual trend of XCH4 of more than 9.50 ppb yr−1, with a minimum rate of 8.72 ± 0.3 ppb yr−1 over Wular Lake. The WetCHARTs-based emissions of CH4 from the wetlands were minimal during the winter and pre-monsoon seasons. Maximum CH4 emissions were reported during the monsoon, with a maximum value of 23.62 ± 3.66 mg m−2 per month over the Sundarbans Wetland. For the 15 Indian agroclimatic zones, significant high emissions of CH4 were observed over the Middle Gangetic Plain, Trans-Gangetic Plain, Upper Gangetic Plain, Eastern Coastal Plains, Lower Gangetic Plain, and East Gangetic Plain. Further, the bottom-up anthropogenic CH4 emissions data are mapped against the XCH4 concentrations, and a high correlation was found in the Indo-Gangetic Plain region, indicating the hotspots of anthropogenic CH4.

Tryptamine-Derived Schiff Bases: Potent Antimicrobial Agents and Evaluation of Cytotoxicity, ADME and DNA Binding Properties.

Inspired by the fact that the introduction of indole pharmacophore in organic scaffolds could enable interesting pharmacological properties, the series of novel tryptamine-derived Schiff bases was synthetized. Tryptamine was used as a source of indole pattern, as well as an example of biogenic amines which chemical transformations lead to the compounds with prominent biological activities. The obtained results for antimicrobial activity against a range of bacterial and fungal strains and cytotoxic activities have revealed that Schiff base TSB4 combining the tryptamine and p-nitro aryl patterns in the structure showed better antifungal activity at low concentrations than standard drug Fluconazole, while compound TSB6 with molecular scaffold composed from tryptamine and quinoline moieties showed certain cytotoxic effect on HCT-116 cell line with a strongly expressed selectivity about healthy fibroblast cells, MRC-5. For these two selected compounds, additional ADME analysis and DNA interactions were performed. to obtain better insight into their pharmacokinetics and determination of binding mode for DNA molecules. As results suggested, strong binding of examined compounds to CT-DNA was observed, while the ADME screening showed that selected compounds possess suitable physicochemical properties for oral bioavailability and druglikeness.

Modular Assembly of Heterotrifunctional Molecules Enabled by Iodosulfonylation of Allenes and Subsequent Amination.

Beyond the rapid achievements of therapeutic heterobifunctional molecules, some recent efforts have focused on constructing heterotrifunctional molecules, aiming at developing more potent and selective therapeutic agents or emerging additional functions to heterobifunctional molecules. However, the synthesis of these complex molecules requires a specific design and lengthy steps. We have developed a two-step strategy for the modular construction of heterotrifunctional molecules, enabled by the sustainable and convenient iodosulfonylation of allenes followed by SN2'-selective amination. This strategy successfully incorporates a broad range of biologically active molecules, labeling them with a fluorescent group. The applications of the obtained compounds in selective protein labeling, subcellular imaging, and targeted inhibition of tumor cells make this strategy highly appealing.

Marine Cyanobacteria-Assisted Metallic Nanoparticles: A Review on Anticancer Activity and Mechanism of Action

Marine cyanobacteria, known as blue-green algae, are ancient microorganisms with oxygenic photosynthetic capability. They have diverse biochemical capabilities, including production of bioactive secondary metabolites. We studied the anti-cancer properties of cyanobacterial nanoparticles through various literatures. We focused on mechanistic studies of the anticancer properties of metal and metal oxide nanoparticles. Our research gathered information from patent databases, conference abstracts, publications, and news releases, as well as PubMed searches for peer-reviewed articles and Google searches for gray literature. We used strict criteria for selecting sources, and our search ended on 30 October, 2022. Metal nanoparticles, such as gold and silver, have unique physicochemical properties, making them suitable for therapeutic applications in nanomedicine. Cyanobacteria-assisted synthesis is environmentally sustainable and results in mild reaction conditions and minimal toxic byproducts. These nanoparticles have potential applications in cancer therapy, including drug delivery systems and targeted therapies. This study further explored the mechanistic aspects of cancer development, emphasising the role of genetic mutations, uncontrolled cell growth, and metastasis. Cyanobacterial biogenic nanoparticles demonstrate cytotoxicity, apoptosis induction, ROS generation, and immunomodulation, contributing to their anticancer efficacy. Additionally, these nanoparticles serve as carriers for drug delivery, enabling the targeted and controlled release of therapeutic agents. The review ends by emphasising how crucial it is to comprehend how cyanobacteria extract assists metallic nanoparticles. Cyanobacterial biogenic synthesis using microemulsion synthesis methods, UV-initiated photoreduction, microwave assistance, and polymer/polysaccharide-mediated approaches was investigated. The field of marine cyanobacteria, biogenic metal nanoparticles, and their anticancer potential is dynamic and has important implications for future therapeutic approaches.

Exploring northeast India’s culturable soil Actinomycetia for potent antibacterial agents against gram-positive bacterial pathogens of clinical importance

This study investigated the isolation and bioactivity of Actinomycetia from the soil of Northeast India, a region rich in microbial diversity. A total of 187 presumptive Actinomycetia isolates were obtained and 53 were found to exhibit antimicrobial properties. Phylogenetic analysis based on 16 S rRNA gene sequencing revealed that the isolates were predominantly from the genus Streptomyces. Among these, the strain Streptomyces sp. NP14 (ANP14ARS) demonstrated specific and significant antimicrobial activity against gram-positive bacterial pathogens. The strain was further assayed against a panel of clinically important bacterial pathogens including Methicillin-resistant Staphylococcus aureus (MRSA). Its antimicrobial activity was confirmed using disc diffusion and membrane disruption assay, and its minimum inhibitory concentration was determined to be ≥ 3.12 ± 0.5 µg/ml against MRSA. Chemical analyses using FTIR and GC-MS identified key bioactive compounds, including Pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl)- and Phenol 3,5-bis(1,1-dimethylethyl), known for their antimicrobial properties. Toxicity studies against animal liver cell lines indicated that the ethyl acetate extract was non-toxic at concentrations below 125 µg/mL, compared to Vancomycin, which was found to be hepatotoxic at similar concentrations. These findings highlight the potential of ANP14ARS as a source of bioactive natural products that is specific towards priority pathogens such as MRSA.

Discovery of novel 2,4-diarylaminopyrimidine hydrazone derivatives as potent anti-thyroid cancer agents capable of inhibiting FAK

In this work, thirty 2,4-diarylaminopyrimidine-based hydrazones were designed, synthesised, and their anti-thyroid cancer activity were explored. The majority of compounds exhibit moderate to excellent cytotoxic activity against FAK overexpressing TPC-1 cells, with IC50 values ranging from 0.113 to 1.460 μM. Among them, compound 14f displayed exceptional anti-proliferative effect against TPC-1 cells (IC50 = 0.113 μM) and potent FAK inhibitory potency (IC50 = 35 nM). In silico studies indicated that compound 14f could well bind to FAK (Focal Adhesion Kinase) and have favourable pharmacokinetic profiles. In addition, compound 14f could inhibit the phosphorylation of FAK at Tyr397, Tyr576/577 and Tyr925, and did not affect the expression level of FAK in TPC-1 cells. Compound 14f was also effective in inhibiting the proliferation and migration of thyroid cancer cells TPC-1. Thus, these novel 4-arylaminopyrimidine hydrazone derivatives exhibited potent anti-thyroid cancer activities through the inhibition of FAK.

JIB-04, an inhibitor of Jumonji histone demethylase as a potent antitubercular agent against Mycobacterium tuberculosis.

The increasing drug resistance of Mycobacterium tuberculosis (Mtb), coupled with the limited availability of effective anti-tuberculosis medications, poses significant challenges for the management and treatment of tuberculosis (TB). Globally, non-tuberculous mycobacteria (NTM) infections are increasing, with Mycobacterium avium complex and Mycobacterium abscessus (Mab) being the most common in labs and having few treatment options. There's an urgent need for innovative therapies against Mtb and NTM that are effective and have minimal side effects. The study evaluated the in vitro efficacy of JIB-04, a Jumonji histone demethylase inhibitor, against Mtb, Mab, and multidrug-resistant (MDR) clinical isolates using the minimum inhibitory concentration (MIC) assay. We also determined the minimum bactericidal concentrations (MBCs) of JIB-04 against the H37Rv and H37Ra strains. A time-kill assay was performed to assess the comparative efficacy of JIB-04 and rifampicin against H37Ra. Additionally, the study investigated the impact of JIB-04 on biofilm formation and the persistence of H37Ra over extended periods. Our findings demonstrated a substantial inhibitory effect of JIB-04 on the growth of Mab, Mtb, and MDR clinical isolates. JIB-04 showed bactericidal effects at twice the MIC, outperforming rifampicin in reducing viable cell counts over 8 days. It showed moderate cytotoxicity to mammalian cells but effectively inhibited biofilm formation. In our anoxia model, JIB-04 induced a significant, concentration-dependent reduction in bacterial load. JIB-04 is a promising candidate for the treatment of MDR tuberculosis.

Comparison of Different Concentrations of Antibiotics with Nanoparticles Synthesized by Biological Method on Pseudomonas aeruginosa Isolated from The Surface

Background: The widespread and indiscriminate use of antibiotics, disinfectants, and antiseptics in medical centers has led to the emergence of resistance in Pseudomonas aeruginosa, a major cause of hospital infections. Objectives: This study aims to compare the effects of antibiotics—cotrimoxazole, cephalexin, cefotaxime, cefazolin, gentamicin, imipenem, ampicillin, and ceftazidime—with silver nanoparticles synthesized in medicinal plant extract against Pseudomonas aeruginosa bacteria. Methods: Ten antibiotic-resistant strains of Pseudomonas aeruginosa were isolated from surfaces at the maternity hospital of Amir al-Mominin Hospital in Zabul city. In this study, nanoparticles were synthesized using an aqueous extract of the medicinal plant Capparis. The minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC) of the synthesized nanoparticles and antibiotics were determined by the microdilution method. Results: The minimum inhibitory concentrations for the antibiotics ceftriaxone, cephalexin, cotrimoxazole, gentamicin, cefotaxime, imipenem, ceftazidime, ampicillin, and cefazolin were 128, 64, 32, 16, 4, 64, 64, 8, and 64 µg/mL, respectively. The minimum inhibitory concentration for the synthesized silver nanoparticles was 1024 μg/mL, with inhibition observed in four strains at this concentration. Conclusions: This study demonstrated good antimicrobial effects of synthesized silver nanoparticles on Pseudomonas aeruginosa. Therefore, silver nanoparticles may be recommended as a potent antimicrobial agent for disinfecting hospital surfaces.

Drug repurposing of fluoroquinolones as anticancer agents in 2023.

Drug developers are currently focusing on investigating alternative strategies, such as "drug repositioning", to address issues associated with productivity, regulatory obstacles, and the steadily rising cost of pharmaceuticals. Repositioning is the best strategy to stop searching for new drugs because it takes less time and money to investigate new indications for already approved or unsuccessful drugs. Although there are several potent Topo II inhibitors available on the market as important drugs used in the therapy of many types of cancer, more may be required in the future. The current inhibitors have drawbacks including acquired resistance and unfavorable side effects such as cardiotoxicity and subsequent malignancy. A substantial body of research documented the cytotoxic potential of experimental fluoroquinolones (FQs) on tumor cell lines and their remarkable efficacy against eukaryotic Topo II in addition to optimized physical and metabolic characteristics. The FQ scaffold has a unique ability to potentially resolve every major issue associated with traditional Topo II inhibitors while maintaining a highly desirable profile in crucial drug-likeness parameters; therefore, there is a significant chance that FQs will be repositioned as anticancer candidates. This review offers a summary of the most recent research on the anticancer potential of FQs that was published in 2023. Along with discussing structural activity relationship studies and the mechanism underlying their antiproliferative activity, this review aims to provide up-to-date information that will spur the development of more potent FQs as viable cancer treatment candidates.