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In vitro analysis of the anticancer and antimicrobial potentials and phytochemical profiles of leaf extracts from five Vachellia species.

The prevalence of antimicrobial resistance and cancer is on the rise, and these ailments create difficulties in therapeutic management and p … w lower cytotoxicity to MRC-5 normal cells (IC₅₀ > 20 μg/mL), thus indicating good selectivity with camptothecin used as a positive control. V. karroo showed cytotoxic activity with IC₅₀ values of 9.61 ± 1.00 and 3.51 ± 1.05 μg/mL against MCF-7 and HCT116 cells, while camptothecin exhibited IC₅₀ values of 5.52 ± 0.70, 6.52 ± 0.76 and 4.60 ± 0.56 μg/mL against …

Valine-Alanine-Based Peptidomimetic Linker for Antibody-Drug Conjugates.

Antibody-drug conjugates (ADCs) hold immense potential for novel linker modifications. However, the instability of current ADC peptide linkers in long-term in vivo circulation can lead to premature toxin release and safety concerns. This study explored novel peptidomimetic ADCs, which linker were created by introducing a triazole group next to its valine-alanine (-VA-) chain via click chemistry. The highly active camptothecin molecule 11b developed in our laboratory was selected as the payload for evaluation, subsequently yielding the preferred ADC compounds Tras-TL1 and Tras-TS2 to verify the…

Novel Lomefloxacin-Triazole Hybrids: Design, Synthesis and In Vitro Antiproliferative Activity in Breast, Melanoma and Colon Cancer Cell Lines.

In recent years, extensive research has focused on fluoroquinolone-triazole hybrids, with particular emphasis on structural modifications of ciprofloxacin. In the present study, novel derivatives of lomefloxacin with a 1,4-disubstituted-1,2,3-triazole moiety were designed, synthesised, and biologically evaluated at the N4 position of the piperazine ring. Molecular docking studies suggested potential interactions of the designed compounds with topoisomerase I, with docking scores comparable to that of the reference compound camptothecin. Molecular dynamics simulation suggested short-term confor…

SLX1 Inhibition Enhances Olaparib Sensitivity by Impairing Homologous Recombination Repair in Breast Cancer.

While PARP inhibitors like Olaparib are effective against BRCA1-deficient breast cancers, their efficacy in BRCA1-proficient tumors depends … instability, and sensitizes breast-proficient breast cancer cells to DNA-damaging agents, including camptothecin, ionizing radiation, and Olaparib. In contrast, SLX1 overexpression enhances DNA repair capacity and promotes Olaparib resistance. In vivo, SLX1 knockdown synergizes with Olaparib to suppress tumor growth in xenograft models. These findings establis …

Rational Design of Bioinspired Lipoprotein System to Improve Penetration in Colorectal Peritoneal Metastases.

Chemotherapy of lethal colorectal peritoneal metastases (PM) is notoriously challenged by poor drug delivery efficiency in PM tumors. Inspired by the histopathological examinations of PM tumors from colon cancer patients, a C[RGDfK] peptide-modified bioinspired lipoprotein (R-BLP) system was optimized from 8 formulations with profound penetrating ability in PM tumors of colorectal cancers. Then, a chemotherapeutic 7-ethyl-10-hydroxy-camptothecin (SN38)-loaded R-BLP (termed SR-BLP) was designed to promote their penetration in PM tumors and improve the chemotherapeutic efficacy. In CT26-induced …

One-Pot Synthesis of Aminodiperoxides from 1,5-Diketones, Geminal Bishydroperoxides and Ammonium Acetate.

Herein, we report an efficient one-pot synthesis of bridged aminodiperoxides via a three-component reaction of 1,5-diketones with geminal bi … and A549 cancer cell lines, and are significantly superior to the clinically used anticancer agent camptothecin. Among all tested compounds, 3ec is the most promising candidate, exhibiting high activity and selectivity toward all tested cell lines (Jurkat: CC50 = 12.9 µM, SI = 67.09; K562: CC50 = 19.6 µM, SI = 44.28; A549: CC50 = 48.2 µM, SI = 17.98). Further …

A dual-responsive AI-designed peptide P9-conjugate disrupts E6-E6AP Interface to restore p53 and suppress HPV16-driven cervical cancer.

Cervical cancer remains a major global health burden in women, mainly driven by persistent infection with high-risk human papillomavirus (hr … an optimized peptide (P9) with high affinity for E6. P9 is further conjugated to chemotherapy drug camptothecin (CPT) to form a dual-responsive compound (Comp.1) with enhanced intracellular delivery, disruption of E6-E6AP interaction, and restoration of p53 function. Our work offers an effective and selective way to interfere with HPV-driven cervical cancer a …

Novel Pyrido[2',1':2,3]imidazo[4,5-c]quinoline Derivative Selectively Poisons Leishmania donovani Bisubunit Topoisomerase 1 to Inhibit the Antimony-Resistant Leishmania Infection in Vivo.

The unique bisubunit structure of Leishmania donovani topoisomerase 1B (LdTop1) is a potential drug target in the parasites unlike the monom … rtantly, the human Top1 is not sensitive to C17. Further, C17 overcomes the chemical instability of camptothecin (CPT) by generating persistent LdTop1cc-induced DNA breaks inside the parasites even after 12 h of drug removal. Intraperitoneal administration of C17 results in marked reduction of the Leishmania amastigotes from the infected spleen and liver of BA …

FACS-based genome-wide CRISPR screens define key regulators of DNA damage signaling pathways.

DNA damage-activated signaling pathways are critical for coordinating multiple cellular processes, which must be tightly regulated to mainta … covered that proteasome-mediated processing is an early and prerequisite event for cells to trigger camptothecin- and etoposide-induced DDR signaling. Furthermore, we identified PRMT1 and PRMT5 as modulators that regulate ATM protein level. Moreover, we discovered that GNB1L is a key regulator of DDR signaling via its role as a co-chaperone specifically regula …

Mono- and binuclear complexes of copper(II) with dimethylaminomethyl derivatives of 2-naphthol and 6-quinolinol: synthesis and in vitro study of antitumor properties.

1-(Dimethylamino)methyl-6-quinolinol scaffold, a structural moiety of the molecule of anticancer drug topotecan, was modified into copper-co … nolligand. All synthesized Cu(II) complexes had higher antitumor activity than the drugs topotecan, camptothecin, and platinum containing cisplatin.

Pulmonary delivery of liposomes co-loaded with SN38 prodrug and curcumin for the treatment of lung cancer.

A co-delivery system of SN38 (7-ethyl-10-hydroxyl camptothecin) prodrug and CUR (curcumin) was designed for the treatment of lung cancer by pulmonary delivery. SN38 was linked to cell-penetrating peptide (CPP) TAT via a polyethylene glycol (PEG) linker to form the SN38 prodrug (TAT-PEG-SN38). Liposomes co-loaded with amphiphilic TAT-PEG-SN38 and curcumin (Lip-TAT-PEG-SN38/CUR) were successfully prepared by a microfluidic method for the treatment of lung cancer via pulmonary delivery. Lip-TAT-PEG-SN38/CUR showed nanometer-sized sphericity and a particle size of 171.21 nm. Besides, Lip-TAT-PEG-S…

Diffuse alveolar damage after a single dose of topotecan in a patient with pulmonary fibrosis and small cell lung cancer.

Drug-induced pulmonary toxicities of anticancer agents have been well described, but the pathophysiology of agents typically used in advance … veolar damage in a patient developing dyspnea following topotecan therapy. The frequency with which camptothecin-related dyspnea is associated with diffuse alveolar damage might be underestimated and is of special concern in patients with limited pulmonary reserve.

Hypoxia induces p53 through a pathway distinct from most DNA-damaging and stress-inducing agents.

The p53 tumour suppressor gene is a transcription factor that can induce cell cycle arrest and apoptosis. In response to various stress-indu … 3 by a variety of stress-inducing agents in vivo, such as 5-fluorouracil, doxorubicin, mitomycin C, camptothecin and roscovitine. However, caffeine failed to affect the accumulation of p53 in hypoxia (HYP)-treated cells. These results suggested that HYP must use a distinct pathway from most DNA-damaging and stress-inducing agents to induce p53.

Antitumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumor/medulloblastoma models as single agent and in combination chemotherapy.

We examined the cytotoxicity of the immunosuppressant agent rapamycin and its analogue CCI-779 in human brain tumor cell lines in vitro and in vivo as single agents and in combination with standard chemotherapeutic drugs. In the rapamycin-sensitive PNET/MB cell line DAOY, rapamycin exhibited additive cytotoxicity with cisplatin and with camptothecin. In vivo, CCI-779 delayed DAOY xenograft growth by 160% after 1 week and 240% after 2 weeks of systemic treatment, compared with controls. Single high-dose treatment induced 37% regression of tumor solume. Growth inhibition of DAOY xenografts was 1…

Glycosylphosphatidylinositol (GPI)-deficient Jurkat T cells as a model to study functions of GPI-anchored proteins.

Many cell surface proteins attached to the membrane by GPI are involved in cell signalling. However, the role of the GPI membrane anchor its … n and survival were not affected by this difference. Apoptotic stimuli such as serum starvation and camptothecin exposure elicited similar responses. In contrast, GPI-defective Jurkat cells were more susceptible to Fas-mediated apoptosis than GPI-positive cells. These results indicate that a deficiency in GPI-anchored proteins, as is found in PNH, does not con …

Influence of Ca2+ depletion on cytoskeleton and nucleolus morphology in Trypanosoma brucei.

Trypanosoma brucei bloodstream forms were incubated in a calcium-free medium containing 10 microM ethyleneglycol-bis-(beta-aminoethyl ether) … vely. Nucleolus segregation, but not microtubule accumulation, was also obtained by using 20 microM camptothecin, a specific inhibitor of topoisomerase I. Our data suggest that intracellular calcium regulation might be important for specific depolymerization/polymerization reactions during the course of cell division and the formation of functional ribosomes.

Visualizable, AKR1C3-Activated Small-Molecule Antitumor Drug Conjugates with Ultra-Low Systemic Toxicity.

Developing targeted antitumor agents with minimal systemic toxicity is highly desirable. Exatecan, a potent camptothecin derivative, is clinically restricted due to its toxicity and limited efficacy. Targeting the tumor-enriched enzyme AKR1C3 enables selective drug activation. We designed two novel AKR1C3-responsive Exatecan conjugates, EP-1 and EP-2, with a fluorescence-quenched module for real-time "turn-on" tracking of drug release. The conjugates exhibited potent cytotoxicity in AKR1C3-high cancer cells (IC50: 7.7 ± 0.2 nM for EP-1, 4.6 ± 0.4 nM for EP-2), similar to Exatecan, but markedly…

A sphingolipid-derived paclitaxel nanovesicle enhances efficacy of combination therapies in triple-negative breast cancer and pancreatic cancer.

Taxol and Abraxane, the US Food and Drug Administration-approved paclitaxel (PTX) formulations, have revealed hypersensitivity due to excipi … us promising PTX nanoformulations. Finally, the series of nanoparticle modifications was applied to camptothecin, demonstrating its generalizability.

Unique Polyester-Based Biodegradable Multiarm Nano-Carrier for Cancer Cell Specific Mitochondrial Delivery of Chemotherapeutics.

Biodegradable polymeric nanocarriers hold significant potential for various biomedical applications, enabling the targeted and controlled delivery of drugs and bioactive molecules. In this context, pendant-functionalized polycaprolactone has garnered tremendous attention over the past few decades. Herein, we developed a mitochondria-targeted polycaprolactone-based polyprodrug, TPP PCL CPT PEG BTN, for the site-specific delivery of camptothecin (CPT). The design incorporates triphenylphosphonium (TPP+) and tertiary amine moieties for mitochondrial targeting, biotin (BTN) for receptor-mediated u…

Три связанных с E2F сигнатуры мишеней для прогнозирования прогноза, иммунных особенностей и чувствительности к лекарствам в гепатоцеллюлярной карциноме.

Фон: гепатоцеллюлярная карцинома (ГХЦ) является чрезвычайно злокачественной и трудной в лечении. Считается, что основным направлением роста опухолей является аденовальный ранний регион 2, связывающий факторы (E2F). Цель этого исследования состояла в том, чтобы определить прогнозируемую целевую сигнатуру E2F и облегчить индивидуальное лечение пациентов КЦУК. Методы: Мы создали целевые генные характеристики, связанные с E2F, с использованием однократных моделей регрессии COX и LASSO и доказали их прогнозируемую эффективность в внешних группах. Кроме того, мы описали роль целевого направления E2F

Совпадение в аннотации оригинала
Background: Hepatocellular carcinoma (HCC) is extremely malignant and difficult to treat. The adenoviral early region 2 binding factors (E2F … rvival time, immune evasion, tumor stem cell characteristics and high sensitivity to Tipifarnib and Camptothecin drugs. Conclusion: Hepatocellular carcinoma prognosis was predicted by an E2F target signature. This finding establishes the theoretical usefulness of the E2F target route in customized identification and treatment for future research.