Synthesis and in-vitro anti-proliferative with antimicrobial activity of new coumarin containing heterocycles hybrids DOI Creative Commons

Eman Abdelaziz,

Nehal M. El‐Deeb, Mervat F. Zayed

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Dec. 21, 2023

A series of new coumarin-N-heterocyclic hybrids, coumarin-quinolines 7a-e, coumarin-acridines 10b,c and coumarin-neocryptolepines 13b,c were synthesized evaluated for their anticancer antimicrobial activities. The structures all hybrids confirmed by FT-IR, 1H-NMR, 13C-NMR, MS spectrometry. anti-proliferative activity 10c 13c bio-evaluated using MTT-assay against colon (CaCo-2), lung (A549), breast (MDA-MB-231), hepatocellular carcinoma (HepG-2) human cancer cell lines doxorubicin as a reference drug. results demonstrated that, displayed moderate to good the lines. most active 7a-d CaCo-2 line with IC50: 57.1, 52.78, 57.29, 51.95 56.74 µM, selectivity index 1.38, 1.76, 2.6, 1.96 0.77; respectively. While, 7a,d potent A549 51.72, 54.8 µM 1.5, 0.67; Moreover, 7c showed potency MDA-MB-231 50.96 2.20. Interestingly, docking revealed that binding energy current compounds marked affinity values ranging from -6.54 -5.56 kcal interactions reported key amino acid SER 79. Furthermore, 10b,c, 13b Gram-positive Gram-negative bacterial fungal strains. 10b, 13b, 10c, exhibited broad-spectrum antibacterial E.coli, S. mutans, aureus MIC 3.2 66 this also antifungal C. albicans 0.0011 29.5 µM. In-silico investigation pharmacokinetic properties indicated tested had high GI absorption, low Blood Brain Barrier (BBB) permeability in addition membrane penetrability.

Language: Английский

Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer DOI
Marilyne Labrie, Joan S. Brugge, Gordon B. Mills

et al.

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(6), P. 323 - 339

Published: March 9, 2022

Language: Английский

Citations

227
Overcoming Cancer Multi-drug Resistance (MDR): Reasons, mechanisms, nanotherapeutic solutions, and challenges DOI Open Access
Chunyan Duan, Mingjia Yu,

Jiyuan Xu

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 162, P. 114643 - 114643

Published: April 7, 2023

Multi-drug resistance (MDR) in cancer cells, either intrinsic or acquired through various mechanisms, significantly hinders the therapeutic efficacy of drugs. Typically, reduced performance drugs is predominantly due to inherent over expression ATP-binding cassette (ABC) transporter proteins on cell membrane, resulting deprived uptake drugs, augmenting drug detoxification, and DNA repair. In addition physiological abnormalities extensive blood flow, MDR phenotypes exhibit improved apoptotic threshold efflux efficiency. These severe consequences have substantially directed researchers fabrication advanced strategies, such as co-delivery along with generations inhibitors, augmented dosage regimens frequency administration, well combinatorial treatment options, among others. this review, we emphasize different reasons mechanisms responsible for cancer, including but not limited known mediated by permeability glycoprotein (P-gp) other pumps, uptake, altered repair, targets, Further, an emphasis specific cancers that share pathogenesis executing effluxed common provided. Then, aspects related nanomaterials-based supramolecular programmable designs (organic- inorganic-based materials), physical approaches (light- ultrasound-based therapies), are discussed, highlighting unsolved issues future advancements. Finally, summarize review interesting perspectives trends, exploring further opportunities overcome MDR.

Language: Английский

Citations

132
Precision oncology for BRAF-mutant cancers with BRAF and MEK inhibitors: from melanoma to tissue-agnostic therapy DOI Creative Commons
Mohamed A. Gouda, Vivek Subbiah

ESMO Open, Journal Year: 2023, Volume and Issue: 8(2), P. 100788 - 100788

Published: Feb. 25, 2023

Language: Английский

Citations

58
Harnessing machine learning to find synergistic combinations for FDA-approved cancer drugs DOI Creative Commons
Tarek Abd El‐Hafeez, Mahmoud Y. Shams, Yaseen A. M. M. Elshaier

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 29, 2024

Abstract Combination therapy is a fundamental strategy in cancer chemotherapy. It involves administering two or more anti-cancer agents to increase efficacy and overcome multidrug resistance compared monotherapy. However, drug combinations can exhibit synergy, additivity, antagonism. This study presents machine learning framework classify predict combinations. The utilizes several key steps including data collection annotation from the O’Neil interaction dataset, preprocessing, stratified splitting into training test sets, construction evaluation of classification models categorize as synergistic, additive, antagonistic, application regression combination sensitivity scores for enhanced predictions prior work, last step examination features mechanisms action understand synergy behaviors optimal identified pairs most likely synergize against different cancers. Kinase inhibitors combined with mTOR inhibitors, DNA damage-inducing drugs HDAC showed benefit, particularly ovarian, melanoma, prostate, lung colorectal carcinomas. Analysis highlighted Gemcitabine, MK-8776 AZD1775 frequently synergizing across types. provides valuable approach uncover effective multi-drug regimens.

Language: Английский

Citations

42
Targeted Therapeutic Strategies for the Treatment of Cancer DOI Open Access

Benjamin Victoir,

Cécile Croix,

Fabrice Gouilleux

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(2), P. 461 - 461

Published: Jan. 22, 2024

Extensive research is underway to develop new therapeutic strategies counteract therapy resistance in cancers. This review presents various achieve this objective. First, we discuss different vectorization platforms capable of releasing drugs cancer cells. Second, delve into multitarget therapies using drug combinations and dual anticancer agents. section will describe examples that have been used treat solid tumors.

Language: Английский

Citations

23
Molecular principles underlying aggressive cancers DOI Creative Commons
Ruth Nussinov, Bengi Ruken Yavuz, Hyunbum Jang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 16, 2025

Language: Английский

Citations

3
Learn from antibody–drug conjugates: consideration in the future construction of peptide-drug conjugates for cancer therapy DOI Creative Commons

Mo Wu,

Wei Huang, Nan Yang

et al.

Experimental Hematology and Oncology, Journal Year: 2022, Volume and Issue: 11(1)

Published: Nov. 8, 2022

Cancer is one of the leading causes death worldwide due to high heterogeneity. Although chemotherapy remains mainstay cancer therapy, non-selective toxicity and drug resistance mono-chemotherapy incur broad criticisms. Subsequently, various combination strategies have been developed improve clinical efficacy, also known as cocktail therapy. However, conventional "cocktail administration" just passable, potential toxicities normal tissues unsatisfactory synergistic effects, especially for combined drugs with different pharmacokinetic properties. The conjugates through coupling chemotherapeutics a carrier (such antibody peptide) provide an alternative strategy therapeutic efficacy simultaneously reduce unspecific toxicities, by virtue advantages highly specific targeting ability potent killing effect. 14 antibody-drug (ADCs) approved more are being investigated in trials so far, several limitations disclosed during application. Compared ADCs, peptide-drug (PDCs) possess advantages, including easy industrial synthesis, low cost, tissue penetration fast clearance. So only handful PDCs approved, highlighting tremendous development potential. Herein, we discuss progress pitfalls ADCs underline what can learn from better construction future.

Language: Английский

Citations

39
CAR T cell-based immunotherapy and radiation therapy: potential, promises and risks DOI Creative Commons
Lusine Hovhannisyan, Carsten Riether, Daniel M. Aebersold

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: May 12, 2023

Abstract CAR T cell-based therapies have revolutionized the treatment of hematological malignancies such as leukemia and lymphoma within last years. In contrast to success in cancers, solid tumors with cells is still a major challenge field attempts overcome these hurdles not been successful yet. Radiation therapy used for management various decades its therapeutic role ranges from local priming agent cancer immunotherapy. Combinations radiation immune checkpoint inhibitors already proven clinical trials. Therefore, combination may potential current limitations cell tumor entities. So far, only limited research was conducted area radiation. this review we will discuss risks patients.

Language: Английский

Citations

35
Drug Delivery Systems for Localized Cancer Combination Therapy DOI
Ryan N. Woodring, Elizabeth G. Graham-Gurysh, Eric M. Bachelder

et al.

ACS Applied Bio Materials, Journal Year: 2023, Volume and Issue: 6(3), P. 934 - 950

Published: Feb. 15, 2023

With over 2 million cancer cases and 600,000 cancer-associated deaths predicted in the U.S. for 2022, this life-debilitating disease continuously impacts lives of people across nation every day. Therapeutic treatment options have historically involved chemotherapies to eradicate tumors with cytotoxic mechanisms which can negatively affect efficacy versus toxicity ratio treatment. a need more directed therapeutically active options, targeted small-molecule inhibitors immunotherapies since emerged mitigate treatment-associated toxicities. However, aggressive employ wide range defense evade monotherapy altogether, resulting recurrence resistant tumors. Therefore, many clinical routines included combination therapy anticancer agents are combined provide synergistic attack on Even approach, maximizing is contingent upon dose drug that reaches site tumor, so often administered at tumor via localized delivery platforms. Commonly used platforms include polymeric wafers, nanofibrous scaffolds, hydrogels where combinations be loaded delivered synchronously. Attaining activity from these systems dependent proper material selection fabrication methods. Herein, we describe important considerations enhancing through biodegradable, systems.

Language: Английский

Citations

32
Deciphering JAK/STAT signaling pathway: A multifaceted approach to tumorigenesis, progression and therapeutic interventions DOI
Yihui Wang, Zhe Wang, Shuyu Li

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 131, P. 111846 - 111846

Published: March 23, 2024

Language: Английский

Citations

15