Zolpidem (Z1) and zopiclone (Z2) are widely prescribed for insomnia; but their misuse in drug-facilitated crimes presents significant forensic and clinical challenges. This study aimed to develop and validate a simple and sensitive LC-MS/MS method, coupled with dispersive liquid-liquid microextraction (DLLME), for the simultaneous determination of Z1, Z2, and 18 phase I and phase II metabolites (20 species) in human urine. DLLME employed 1 mL of dichloromethane as extractant and 2 mL of acetonitrile as disperser per 2 mL of urine, reducing halogenated-solvent use compared with conventional liquid-liquid extraction. Chromatographic separation was achieved on a HyPURITY C18 column with water-acetonitrile (70:30, v/v) containing 0.2% formic acid. Z1 and Z2 were validated according to ICH guidelines over 0.1-200 ng/mL, showing linearity (R2 > 0.999), accuracy (96.29%-99.56%), precision (RSD ≤ 3.12%), and recovery (96.12%-98.74%). Because authentic metabolite standards were unavailable, metabolite concentrations were estimated using parent-drug calibration curves and are considered semi-quantitative. In five healthy volunteers, hydroxylated and carboxylated metabolites peaked at 2-12 h and remained detectable up to 84 h. These findings support the method's potential for retrospective urinary screening of Z-drug exposure in forensic and clinical toxicology.

Antimicrobial resistance (AMR) is growing as a silent pandemic, and one of the major causes of this are pharmaceutical pollutants or antibiotics in our aquatic environment. In view of quenching this growing threat of AMR and for ecological health and public safety, there is a critical need for rigorous monitoring and the remediation of aquatic environments from pharmaceutical residues. To address this issue, the present study was designed to develop polyphenol based biomaterial for detecting antibiotics in the aquatic environment. Natural polyphenols, such as quercetin, offer a sustainable and biocompatible foundation for the development of smart nano-platforms capable of addressing these environmental and biomedical challenges. In this study, quercetin-based biomaterial (QB) was synthesized by oxidative coupling assembly reaction and evaluated for their solvent-dependent fluorescence and antibiotic-sensing capabilities. Fluorescence measurements were performed across various organic solvents with ciprofloxacin and doxycycline, at concentrations between 0.002 µM to 300 µM. The binding interactions and molecular-level optical changes, including electronic transitions, were characterized using UV-Visible spectral studies. The biomaterial exhibited a prominent emission peak at 700 nm, with the highest intensity observed in acetonitrile, indicating that polar solvents stabilize the excited state better. The QB demonstrated a consistent, concentration-dependent quenching mechanism for tested antibiotics. Maximum quenching efficiencies at 300 µM reached 98.96

Breast cancer is the most common and deadly cancer affecting women globally. While traditional treatments - surgery, chemotherapeutic agents, radiotherapy - are used, factors damage their effectiveness: tumor heterogeneity, drug resistance, and non-targeted actions on cancer cells. Postbiotics, a newer category of biotics, confer benefits without living microorganisms and show promise against cancer. This review summarizes the link between gut microbiota and BC, postbiotic mechanisms against cancer, and their potential for personalized medicine. Postbiotics modulate the host immune system and inflammation in BC management. They target apoptotic signaling pathways, such as mitochondrial-dependent and death receptor-dependent pathways, interrupt the cell cycle, inhibit cancer cell growth, and regulate immune responses. In cancer, integrative approaches for therapies include microbiome analysis to provide personalized medical treatment, highlighting the microbiome's impact on cancer. Compared to probiotics, postbiotics have advantages, including better bioavailability, stability, and safety profiles. However, research should continue to address clinical evidence and extended studies in their production and application. The use of postbiotics as adjunctive agents in BC treatment has been highlighted for their potential to enhance standard therapy outcomes.

A porous copper gallate bioinspired metal-organic framework (CuGA bio-MOF) has been synthesized using Copper (ll) chloride dihydrate and gallic acid (a polyphenol) under specific experimental environments to evaluate its antioxidant, drug tagging and release features. Initially, synthesized CuGA Bio-MOF has been analysed through various spectroscopic and microscopic techniques. To proceed further in research and gain a better understanding of readers, we have divided research work into two primary objectives: (a) evaluating the antioxidant properties of CuGA bio-MOF using the 2,2-diphenylpicrylhydrazyl (DPPH) assay and (b) exploring the release of the model drug Ibuprofen (IBU) from CuGA bio-MOF in phosphate-buffered saline (PBS). On confirmation of eminent antioxidant property (79.4 %) of pristine CuGA Bio-MOF, the tagging of Ibuprofen (IBU) on Bio-MOF, i.e., IBU@ CuGA Bio-MOF, has been confirmed through intermolecular hydrogen bonding. Our prolonged release of IBU studies endorsed 90 % release of the drug in 150 min at 37 degrees C, pH 7.4 in phosphate buffer saline (PBS) from IBU@ CuGA bio-MOF. Overall, the antioxidant features of CuGA bio-MOF and the drug release profile of IBU@CuGA bio-MOF exhibited potential real-world application as a suitable drug carrier.

Dengue virus (DENV) infection is one of the diseases for which no drug is available for the treatment. The DENV NS2B-NS3 protease is considered to be the prime target for anti-dengue drug development because of its importance in the development of new virus subunits via DENV poly-protein breakdown. Pentacyclic triterpenoids (Lantadenes) from the weed Lantana camara L. and its semi-synthetic congeners have shown a wide array of biological activities in the last two decades. The virtual screening strategy was used on the library of 78 natural and semi-synthetic lantadenes to predict the potent antagonists for the NS2B-NS3 protease enzyme of DENV and their experimental validation by in vitro assay of lead molecules. In the in silico analysis of 78 triterpenoids, two lead molecules (−10.60 and −9.93 kcal/mol) were predicted to be inhibitors of protease (viral) when compared to its reference ligand 1,8-dihydroxy-4,5-dinitroanthraquinone (−5.377 kcal/mol). At the same time, binding affinity, pharmacokinetic, and toxicity profiling, along with molecular dynamics simulations, were studied. The in vitro viral infection inhibition assay inferred that lead molecule 62 exhibited a 60% and 45% reduction in DENV titers at 10 and 5 µM concentrations, respectively. The lead molecule 62 can further be optimized for its pharmacophore and has the potential to be developed as a drug-like molecule.

The natural origin secondary metabolites have been considered as one of the richest source of new chemical entities with vast array of structural diversity and complexity. The natural compounds have played significant and crucial part in the development of number of therapeutic agents for various diseases especially in the cancer and infectious disease segment. The vast structural and molecular diversity of chemicals present in natural sources inspired medicinal chemist from ages to explore the chemotypes for the innovation and design of new pharmaceuticals and chemical entities. The design of diverse libraries of natural product congeners or derivatives can be achieved using various approaches and strategies to expand the natural product frameworks. Modifying common reactive molecular fragments in natural extracts is an effective strategy for creating pharmacologically active compounds. Various extraction and purification techniques, such as high performance liquid chromatography and supercritical fluid extraction along with membrane-based technologies, are employed to isolate these bioactive compounds.Direct crude extract modification of natural products is an interesting and recent strategy to evolve new chemical entities with diversity in structure and pharmacophore. The reactive chemical moieties present in most of the natural products can be engineered chemically by treating them with particular reagents to yield chemically modified extracts or semi-synthetic molecules constituting distinct libraries with enhanced chemo-diversity and improved pharmacology. This review aims to present latest developments in the synthesis of natural product-inspired medicinal compound libraries via direct chemical modification of crude extracts.

Detecting z-drugs, a sedative-hypnotic medication, is also misused for criminal activities. Therefore, the analysis of urine samples is crucial for clinical and forensic purposes. We conducted a study where we developed, validated, and compared an analytical method for simultaneously detecting z-drugs in urine samples. Our approach uses the QuEChERS method for sample preparation, combined with liquid chromatography (LC) and gas chromatography (GC) coupled with tandem mass spectrometry (MS/MS). We optimized the QuEChERS method to effectively extract z-drugs from urine samples while minimizing matrix effects and achieving high recovery rates. After extraction, we split the samples into two parts for analysis using LC-MS/MS and GC-MS/MS. We validated our methods, and the results showed good linearity over a broad concentration range (1-200 ng/mL) for each z-drug. The limits of detection and quantification were within clinically relevant ranges, ensuring sensitivity for detecting z-drugs in urine samples. We compared the two chromatographic techniques by analyzing a set of urine samples spiked with known concentrations of z-drugs using both LC-MS/MS and GC-MS/MS methods and then applied to the real samples. The results were statistically analyzed to assess any significant differences in accuracy and precision above 95 %, and both methods offered reliable and consistent results with the samples as well. In conclusion, our analytical method coupled with both LC-MS/MS and GC-MS/MS using the QuEChERS approach provides a comprehensive and robust solution for the simultaneous detection of z-drugs in urine samples. The choice between the two chromatographic techniques can be based on the specific z-drugs of interest and the required analytical performance. This method holds promise for applications in clinical toxicology, forensic analysis, and monitoring z-drug usage.

In recent years, the development of biomaterials from green organic sources with nontoxicity and hyposensitivity has been explored for a wide array of biotherapeutic applications. Polyphenolic compounds have unique structural features, and self-assembly by oxidative coupling allows molecular species to rearrange into complex biomaterial that can be used for multiple applications. Self-assembled polyphenolic structures, such as hollow spheres, can be designed to respond to various chemical and physical stimuli that can release therapeutic drugs smartly. The self-assembled metallic-phenol network (MPN) has been used for modulating interfacial properties and designing biomaterials, and there are several advantages and challenges associated with such biomaterials. This review comprehensively summarizes current challenges and prospects of self-assembled polyphenolic hollow spheres and MPN coatings and self-assembly for biomedical applications.

Objective: The study aimed to develop microspheres of quercetin by oxidative coupling assembly and these microspheres were used to deliver diclofenac sodium without causing gastrotoxicity. Methods: The oxidative coupling assembly of quercetin was carried out in the presence of copper sulfate to yield quercetin microspheres. The microsphere of quercetin was loaded with diclofenac sodium (QP-Diclo). The carrageenan induced paw edema in rats was used for anti-inflammatory action was studied by using and acetic acid-induced writhing in mice was used to study the analgesic potential of the QP loaded microspheres. The ulcerogenecity and gastrotoxicity comparison was made between diclofenac and QP-Diclo. Results: The oxidative coupling assembly of quercetin resulted in microspheres of 10-20 μm in size, which were loaded with diclofenac sodium (QP-Diclo). The marked anti-inflammatory activity was observed by QP-Diclo treatment using carrageenan induced paw edema (in rats) and better analgesic activity than diclofenac sodium in mice. The administration of QP-Diclo significantly elevated the diminished overall nitrite/nitrate extent and thiobarbituric acid reactive and significantly increased the diminished superoxide dismutase activity in comparison to diclofenac sodium in gastric mucosa. Conclusion: The results suggested that dietary polyphenol quercetin can be converted to microspheres by oxidative coupling assembly and can be used to deliver diclofenac sodium without causing gastrotoxicity.

We report the anticancer activity, structure-activity relationships (SAR), molecular mechanism, and in silico docking studies of nine pentacyclic triterpenoids derived from lantadene A. The NCI-60 cytotoxicity screening of synthesized compounds on 60 human tumor cell lines, representing nine different cancers revealed that compound 6, bearing dual C-3 and C-22 butyryloxy substitutions at the pentacyclic triterpenoid scaffold, displays remarkable potency with mean growth inhibition of 98.7% at 10 μM. The SRB five-dose assay of compound 6 exhibited that it suppresses the growth of all NCI-60 cell lines with a GI50 value in the single-digit micromolar range, except for one. The Western blot analysis revealed that compound 6 inhibits the expression of IKK-β and its down-stream effector NF-κB (p65). Molecular docking analysis of compound 6 with IKK-β showed hydrogen bond interactions with GLN425 and ARG427 and hydrophobic contact with PHE424 residues as the prominent interactions. Molecular dynamics simulation of the docked complex suggested that the complex was fairly stable. Compound 7, possessing the isobutyryloxy groups at the analogous positions of compound 6 was the second-favorable anticancer agent. Conversely, the substitution of the hydroxy group in compounds emerged as the least favorable substitution at both the C-3 and C-22 positions of the pharmacophore. The presence of the 22β-angeloyloxy side-chain, akin to the natural product lantadene A, exhibited moderate favorability for enhanced activity. As a whole, the cytotoxicity data of compounds underscores the preference for linear and extended substitutions at both the C-3 and C-22 positions of the pharmacophore for heightened activity.

Tramadol (TD) has been prescribed frequently in many countries for more than 40 years, but there is a risk of its misuse and trafficking. As a result, drug analysis has numerous legal and socially relevant implications, making it an essential part of modern analytical chemistry. Thus, the method for the detection of TD and its phase I and phase II metabolites in human urine has been developed and validated using a rapid and efficient approach combining liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization. The sample preparation was best performed using dispersive liquid–liquid microextraction. Analysis was performed using an HyPRITY Cl8 column, and isocratic elution with methanol: water (35:65) with 0.2% formic acid was used. TD and its metabolites were detected at 264.2 (TD/M0) with a base peak at 58.2, 250.3758 (M1), 250.3124 (M2), 236.3976 (M3), 222.5361 (M4), and 236.4475 (M5) m/z peaks. TD showed linearity between 0.1 and 160 ng/mL (R2 = 0.9981). The accuracy ranged from 95.56 to 100.21% for the three concentration levels, while the between- and within-day RSD ranged from 1.58 to 3.92%. The absolute TD recovery was 96.29, 96.91, and 94.31% for the concentrations of 5, 50, and 150 ng/mL, respectively. TD’s phase I metabolites, M1–5 along with nine phase II metabolites, such as sulfo- and glucurono-conjugated metabolites, oxidative TD derivatives, and sulfo-conjugated metabolites were also identified in the urine samples. The pharmacokinetics and metabolism data given provide information for the design of possible future research disorders, evaluating drug mechanism and neurotoxicity and for the effective application screening of TD.

Naturally occurring pentacyclic triterpenoids and their semisynthetic analogues have engrossed increasing attention for their anticancer potential and exhibiting promising role in discovery of new anticancer agents. Present study include the semi synthetic modifications of Lantadenes from the weed Lantana carama and their structures delineation by FT-IR, 1H-NMR, 13C-NMR & mass spectroscopy. All the compounds were scrutinized for in vitro cytotoxicity, ligand receptor interaction and in vivo anticancer studies. Most of the novel analogues displayed potent antiproliferative activity against A375 & A431 cancer cell lines and found superior to parent Lantadenes. In particular, 3 beta-(4-Methoxybenzoyloxy)-22 beta-senecioyloxy-olean-12-en-28-oic acid was found to be most suitable compound, with IC50 value of 3.027 mu M aganist A375 cell line having least docking score (-69.40 kcal/mol). Promising anticancer potential of the lead was further indicated by significant reduction in tumor volume and burden in two stage carcinoma model. These findings suggests that the Lantadene derivatives may hold promising potential for the intervention of skin cancers.

The significance and desire for preliminary testing approaches that are straightforward, quick, selective, affordable, and practical for use in the field are highlighted by the increasing enormous amounts of potentially illegal samples being seized worldwide. The “z-drugs,” which include zolpidem, zopiclone, and eszopiclone, are non-benzodiazepine medications used to treat insomnia. z-drugs are short-term solutions for sleeplessness and anxiety but have a long history of abuse and misuse. The extensive list is primarily utilized for drug-facilitated crimes and drug dependence. The presumptive color spot test for z-drugs, such as zolpidem, zopiclone, and eszopiclone, has been created and validated in this study. In the preliminary identification of zolpidem, zopiclone, and eszopiclone, no color spot test has been documented as per the literature. The color spot test is the most essential and routinely used technique for identifying any unknown sample substance. The color test method was proven to provide high-quality, dependable presumptive test findings and satisfy standards for preliminary screening usage. Validation experiments demonstrate that, at room temperature, the color change is specific to the zolpidem, zopiclone, and eszopiclone classes and unaffected by the common cutting agent’s presence. It was discovered that 5, 10, and 6 ppm were the operational limit of detection of the sample present against the reagents 0.1% diphenyl carbazone, aqueous potassium iodoplatinate, and modified cobalt thiocyanate reagent, respectively. The color test is immediate and validated with other substances of a similar category and 10 ppm was the operational limit of detection.

Background Irinotecan is a promising antitumor agent approved by FDA for intravenous use in colon cancer treatment either alone or in combination. It is a topoisomerase inhibitor and by blocking the topoisomerase-I enzyme, it causes DNA damage and results in cell death. However, it lacks selectivity and specificity for tumor cells, resulting in systemic toxicity. Thus, it is essential to reduce its side effects and improve therapeutic efficacy. Objective The study aimed to improve the therapeutic efficacy and minimize the toxic effects of irinotecan by developing a fullerene functionalized biotin drug delivery system and adsorbing irinotecan on the surface of the functionalized fullerene-biotin complex. Methods Fullerene (C-60) has been observed as a potential drug delivery agent and the amine-functionalized C-60-NH2 was synthesized by functionalizing ethylenediamine on the surface of C-60. The PEI functionalized C-60 was further synthesized by polymerization of aziridine on the surface of C-60-NH2. Biotin was attached by an amide linkage to C-60-PEI and the anti-colon cancer drug irinotecan (IRI) was encapsulated (C-60-PEI-Biotin/IRI). The C-60-PEI-Biotin/IRI was characterized and evaluated for in vivo anti-colon cancer activity in rats and the results were compared with the parent drug irinotecan. Results The results showed that C-60-PEI-Biotin/IRI conjugate had a controlled release profile according to in vitro HPLC studies. Moreover in vivo anti-tumor studies suggested that the conjugate proved to be less toxic to vital organs and had high efficacy towards tumor cells. Statistical studies confirmed less tumor index and tumor burden in the case of conjugate when compared to irinotecan. Conclusion It is hypothesized that the conjugate (C-60-PEI-Biotin/IRI) could cross the cell membrane easily through overexpressed biotin receptors on the cell surface of colon cancer cells and showed better efficacy and less toxicity in comparison to IRI in the colon cancer rat model.

The 4-allyl guaiacol is a natural phenolic molecule that has been widely studied for its antioxidant capacity against reactive-oxygen-species-mediated cellular damage. Therefore, we hypothesized that concomitant use of an antioxidant and NSAID may decrease the risk of gastrointestinal toxicity and make the therapy safer. To address the gastrointestinal toxicity of conventional NSAIDs, a new S-naproxen-4-allyl guaiacol chimera (MAS-1696) was computationally developed, chemically synthesized, and tested for anti-inflammatory effectiveness and gastrointestinal safety. The inhibitory potency of MAS-1696 tested against cyclooxygenase-2 (COX2), 15-lipoxygenase-2 (15-LOX2), and lipoxygenase-5 (5-LOX) in vitro revealed a stronger inhibition of COX2. Furthermore, the MAS-1696 chimera increased the COX selectivity index by 23% as compared to the parent compound naproxen, implying higher efficacy and gastric safety. In vivo data showed that MAS-1696 was less likely to cause gastrointestinal harm than naproxen while also exerting anti-inflammatory and analgesic effects equivalent to or superior to naproxen. In conclusion, MAS-1696 is orally active, bio-labile, and crystalline, making it a medication that may be administered orally.

Background: Despite recent advances in the treatment of squamous cell skin cancer (SCSC), the disease persists, and treatment resistance develops. Thus, identifying new targets and developing new therapeutic approaches showing low vulnerability to drug resistance is highly needed. Purpose: This study aimed to reveal a novel targeted phytotherapeutic strategy for SCSC treatment alone or in combination with standard targeted anticancer molecules. Study design: A library of natural products was utilized to identify molecules that inhibit the growth of skin cancer cells. The anticancer potential of the selected compound was evaluated in human skin squamous carcinoma models, in vitro and in vivo. A comprehensive ingenuity pathway analysis (IPA) strategy and molecular biology technology was adopted to investigate the therapeutic mechanisms in human SCSC. Methods: The Matrigel invasion chamber, foci formation and soft agar colony formation assays were employed to study the cells invasion and migration potential in vitro. In vivo antitumor effects were evaluated in DMBA/TPA-induced skin papilloma and A431 human skin squamous carcinoma xenograft tumor models. An integrative IPA was employed to identify mechanisms and protein targets in human SCSC.Compounds synergies were determined by the bliss model and evaluated using human SCSC cell lines and xenograft tumors. Histological staining, immunofluorescence imaging, real-time PCR, Western blots, and flow cytometric analyses were employed to analyze apoptosis and cell signaling mechanisms. Results: We identified (+)-cyanidan-3-ol (CD-3) as a selective compound for inhibiting the growth of SCSC cell lines. CD-3 inhibited tumor growth and burden without apparent toxicity and prolonged the survival of tumor-bearing mice. CD-3 inhibitory effects on SCSC growth are mediated via cell cycle arrest and caspase-dependent apoptosis induction. Mechanistic studies showed that CD-3 activates PP2A via inhibiting CIP2A and produces tumor growth inhibitory effects via promoting dephosphorylation of oncogenic AKT/mTOR signaling proteins in SCSC cells and xenograft tumors in a PP2A dependent manner. Furthermore, the combination of CD-3 and mTOR inhibitors (mTORi) synergistically reduced oncogenic phenotypes. Conclusions: Our study suggests that PP2A activation is an effective strategy for SCSC treatment and the CD-3 and mTORi combination may serve as a promising treatment for SCSC.

Background: Camptothecin is a naturally occurring alkaloid obtained from the stem wood of the Chinese tree, Camptotheca acuminata. It exerts pharmacological effects due to its ability to selectively inhibit the type-I topoisomerase DNA nuclear enzyme. Several semisynthetic analogs of camptothecin have been synthesized to date possessing antitumor activity. Objective: Camptothecin (CPT) is one of the most promising anticancer drugs but it produces various side effects because of its non-selectivity towards cancer cells. To overcome these adverse effects, we synthesized biotin conjugate of camptothecin, which was linked via a self-immolative disulfide linker (CPT-SS-Biotin). Methods: Biotin conjugated camptothecin linked through a disulfide bond was synthesized following schemes, and the structural characterization was carried out. The stability and drug release studies were performed in the presence of glutathione (GSH) while in vitro studies were performed on 4T1 tumor cell lines. In vivo pharmacological investigation was done using an antitumor Wistar rat model. Results: The stability and drug release studies were performed in the presence of glutathione (GSH), and CPT-SS-Biotin was found to be physiologically stable moiety and can only be cleaved in the presence of GSH to release free CPT. The CPT-SS-Biotin showed higher toxicity in the biotin-overexpressing 4T1 tumor cell line with a lower IC50 value (8.44 mu M) compared to camptothecin alone (IC50 > 30 mu M). CPT-SS-Biotin also showed 10.6% higher cellular uptake by cells in comparison to free camptothecin. The CPT-SS-Biotin was delivered to cells by binding to the biotin receptors on the cell surface, followed by energy-dependent endocytosis and internalization to cause cellular toxicity. Conclusion: In-vivo tumor suppression studies and in vitro cell line studies along with serological parameters and histopathological studies showed that conjugate produced a high therapeutic effect and remarkably reduced toxic effects in comparison to free CPT. The results suggested that biotinylation of camptothecin via disulfide linker can be a safe and efficacious method in cancer therapeutics.

Evidence shows that inflammatory responses may encompass the onset of severe depressive illness. Traditionally used licorice contains 18β-glycyrrhetinic acid (18βGA), which has been demonstrated to reduce inflammation and oxidative stress. This study investigates the antidepressant effects of 18βGA and the underlying mechanism in rats exposed to chronic unpredictable mild stress (CUMS). Wistar rats were exposed to CUMS for 36 consecutive days to establish depression. 18βGA (10, 20, and 50 mg/kg) or fluoxetine was given once daily (from day 30 to day 36). Thereafter, behavior parameters (sucrose preference test, forced-swimming test, open-field test, body weight), pro-inflammatory cytokines, neurotransmitters, adrenocorticotropic hormone (ACTH), corticosterone (CORT), and liver biomarkers were studied. Immunohistochemistry and western blot analyses were conducted to investigate the protein's expression. 18βGA (20 and 50 mg/kg) treatment increased sucrose intake, locomotion in the open-field test, decreased immobility time in the forced swim test, and improved body weight in CUMS-exposed rats. The therapy of 18βGA dramatically declined cytokines, ACTH and CORT and improved 5HT and norepinephrine in CUMS rats. Furthermore, BDNF and TrkB proteins were down-regulated in CUMS group, which was increased to varying degrees by 18βGA at doses of 20 and 50 mg/kg. Therefore, 18βGA ameliorates depressive-like behavior persuaded by chronic unpredictable mild stress, decreases neuroinflammation, liver biomarkers, stress hormones, and improves body weight, brain neurotransmitter concentration via activating on BDNF/TrkB signaling pathway in both PFC and hippocampus in rats.

The clinical use of irinotecan (IRI), one of the most commonly used antitumor drugs for colon cancer, is limited by its numerous side effects, and it also lacks selectivity and specificity for tumor cells. When conjugated with fullerenes and biotin, this drug may serve as a drug of choice to reduce these side effects. Fullerenes are an allotropic form of carbon with a closed cage-like structure that can act as a drug carrier, and the presence of biotin makes it a promising targeting agent. In this work, we performed release as well as toxicity comparison studies between pure irinotecan and fullerene-biotin-conjugated irinotecan. The release studies were performed by HPLC (High Performance Liquid Chromatography), while the toxicity studies were performed on a model of colon tumors in gopher rats. All animals were divided into four groups, namely normal, control, test and standard groups. Biochemical parameters and histopathological studies were performed to compare the acute toxicity of irinotecan and the conjugate (C60-PEI-biotin/IRI). It was found that IRI alone was unable to reduce the toxicity caused by DMH (1,2-dimethylhydrazine), whereas its conjugate was able to significantly reduce the toxic effects, which was also evident in the histopathological studies. Therefore, the study suggests that the administration of conjugated IRI reduces toxicity and proves to be a potential candidate for a preventive chemo effect.