Investigation of the Potential Targets behind the Promising and Highly Selective Antileishmanial Action of Synthetic Flavonoid Derivatives DOI
Estela Mariana Guimarães Lourenço,

Fernanda da Silva,

Amarith R. das Neves

et al.

ACS Infectious Diseases, Journal Year: 2023, Volume and Issue: 9(10), P. 2048 - 2061

Published: Sept. 29, 2023

Leishmaniases are among the neglected tropical diseases that still cause devastating health, social, and economic consequences to more than 350 million people worldwide. Despite efforts combat these vector-borne diseases, their incidence does not decrease. Meanwhile, current antileishmanial drugs old highly toxic, safer presentations unaffordable most severely affected human populations. In a previous study by our research group, we synthesized 17 flavonoid derivatives demonstrated impressive inhibition capacity against rCPB2.8, rCPB3, rH84Y. These cysteine proteases expressed in amastigote stage, target form of parasite. However, although compounds have been already described literature, until now, effect any molecules has proven. this work, aimed deeply analyze action set synthetic correlating ability inhibit with Among all derivatives, 11 them showed high activity amastigotes Leishmania amazonensis, also providing safety mammalian host cells. Furthermore, production nitric oxide infected cells treated active protease B (CPB) inhibitors confirms potential immunomodulatory response macrophages. Besides, considering flavonoids as multitarget drugs, investigated other mechanisms. The were selected investigate another biological pathway behind using flow cytometry analysis. results confirmed an oxidative stress after 48 h treatment. data represent important step toward validation CPB target, well aiding new drug discovery studies based on protease.

Language: Английский

Flavonoid Derivatives as New Potent Inhibitors of Cysteine Proteases: An Important Step toward the Design of New Compounds for the Treatment of Leishmaniasis DOI Creative Commons
Estela Mariana Guimarães Lourenço, Juliana Fortes Di Iório,

Fernanda da Silva

et al.

Microorganisms, Journal Year: 2023, Volume and Issue: 11(1), P. 225 - 225

Published: Jan. 16, 2023

Leishmaniasis is a neglected tropical disease, affecting more than 350 million people globally. However, there currently no vaccine available against human leishmaniasis, and current treatment hampered by high cost, side-effects, painful administration routes. It has become United Nations goal to end leishmaniasis epidemics 2030, multitarget drug strategy emerges as promising alternative. Among the compounds, flavonoids are renowned class of natural products, structurally diverse library can be prepared through organic synthesis, which tested for biological effectiveness. In this study, we synthesised 17 flavonoid analogues using scalable, easy-to-reproduce, inexpensive method. All compounds presented an impressive inhibition capacity rCPB2.8, rCPB3, rH84Y enzymes, highly expressed in amastigote stage, target form parasite. Compounds 3c, f12a, f12b were found effective all isoforms. Furthermore, their intermolecular interactions also investigated molecular modelling study. These potent parasite demonstrated low cytotoxic action mammalian cells. results pioneering, representing advance investigation mechanisms behind antileishmanial derivatives. Moreover, have been shown leads design other cysteine protease inhibitors diseases.

Language: Английский

Citations

3
Applications of Pyrrole and Pyridine-based Heterocycles in Cancer Diagnosis and Treatment DOI
Rajdeep Tyagi,

Kanchan Yadav,

Nitin Srivastava

et al.

Current Pharmaceutical Design, Journal Year: 2023, Volume and Issue: 30(4), P. 255 - 277

Published: Dec. 15, 2023

Background:: The escalation of cancer worldwide is one the major causes economy burden and loss human resources. According to American Cancer Society, there will be 1,958,310 new cases 609,820 projected deaths in 2023 United States. It that by 2040, global expected rise 29.5 million per year, causing a death toll 16.4 million. hemostasis regulation cellular protein synthesis their targeted degradation required for normal cell growth. imbalance unbridled growth cells results cancer. DNA needs chemotherapeutic agents treatment, but at same time, efficacy toxicity also need considered successful treatment. Objective:: objective this study review published work on pyrrole pyridine, which have been prominent diagnosis possess anticancer activity, obtain some novel lead molecules improved therapeutic. Methods:: A literature search was carried out using different engines, like Sci-finder, Elsevier, ScienceDirect, RSC etc., small based pyridine helpful inducing apoptosis cells. research findings application these compounds from 2018-2023 were reviewed variety lines, such as breast cancer, liver epithelial etc. Results:: In review, molecules, derivatives, roles treatment cancers, discussed provide insight into structural features responsible analogues with chromeno-furo-pyridine skeleton showed highest activity against compound 5-amino-N-(1-(pyridin-4- yl)ethylidene)-1H-pyrazole-4-carbohydrazides highly potent HEPG2 cell. Redaporfin used cholangiocarcinoma, biliary tract cisplatin-resistant head neck squamous carcinoma, pigmentation melanoma, it clinical trials phase II. These present high potential designing drug development. Conclusion:: Therefore, N- C-substituted pyridine-based privileged Nheterocyclic scaffolds are This discusses reports during 2018-2023. mainly various diagnostic techniques employ heterocyclic scaffolds. Furthermore, has described, works MCF-7, A549, A2780, HepG2, MDA-MB-231, K562, HT- 29, Caco-2 cells, Hela, Huh-7, WSU-DLCL2, HCT-116, HBL-100, H23, HCC827, SKOV3, help researchers critical aspects useful well design pathways develop drugs future.

Language: Английский

Citations

2
Synthesis of silver nanoparticles coupled with aromatic diselenides: greener approach, potential against glioma cells and DNA interaction DOI
Sumbal Saba,

Natália B. Preve,

Isis Juliane Arantes Granja

et al.

New Journal of Chemistry, Journal Year: 2022, Volume and Issue: 47(6), P. 2727 - 2735

Published: Dec. 26, 2022

Synthesis of organochalcogen-modified silver nanoparticles (A1-7), their cytotoxic potentials against glioma cells (C6) & interaction with DNA.

Language: Английский

Citations

3
İMİDAZOPİRİDİN TÜREVLERİNİN KANSER HÜCRE SİNYALİNDEKİ ETKİLERİ DOI Open Access
Hazal Ceylan, Erkan Yurtçu

Kırıkkale Üniversitesi Tıp Fakültesi Dergisi, Journal Year: 2024, Volume and Issue: 26(2), P. 245 - 251

Published: Aug. 20, 2024

Kanser tedavisinde kullanılan konvansiyonel etkinliklerinin sınırlı olması yeni ajanların keşfini gerektirmektedir. İmidazopiridin iskelesine sahip bileşikler çeşitli kimyasal modifikasyonlara açık sebebiyle geliştirilmesi için umut verici potansiyele sahiptir. Hücre içi sinyal yolakları normal hücre fizyolojisinde gerekli olup bozuklukları kanser dahil çok sayıda hastalığın patogenezinde rol oynar. Çok çalışma ile imidazopiridinlerin hücreleri üzerinde sitotoksik ve apoptotik özellikleri gösterilmiş olsa da bu bileşiklerin üzerindeki etkilerini araştırmayı hedeflemiştir. Elde edilen veriler grup yolları etkili olduğunu göstermektedir.

Citations

0
Investigation of the Potential Targets behind the Promising and Highly Selective Antileishmanial Action of Synthetic Flavonoid Derivatives DOI
Estela Mariana Guimarães Lourenço,

Fernanda da Silva,

Amarith R. das Neves

et al.

ACS Infectious Diseases, Journal Year: 2023, Volume and Issue: 9(10), P. 2048 - 2061

Published: Sept. 29, 2023

Leishmaniases are among the neglected tropical diseases that still cause devastating health, social, and economic consequences to more than 350 million people worldwide. Despite efforts combat these vector-borne diseases, their incidence does not decrease. Meanwhile, current antileishmanial drugs old highly toxic, safer presentations unaffordable most severely affected human populations. In a previous study by our research group, we synthesized 17 flavonoid derivatives demonstrated impressive inhibition capacity against rCPB2.8, rCPB3, rH84Y. These cysteine proteases expressed in amastigote stage, target form of parasite. However, although compounds have been already described literature, until now, effect any molecules has proven. this work, aimed deeply analyze action set synthetic correlating ability inhibit with Among all derivatives, 11 them showed high activity amastigotes Leishmania amazonensis, also providing safety mammalian host cells. Furthermore, production nitric oxide infected cells treated active protease B (CPB) inhibitors confirms potential immunomodulatory response macrophages. Besides, considering flavonoids as multitarget drugs, investigated other mechanisms. The were selected investigate another biological pathway behind using flow cytometry analysis. results confirmed an oxidative stress after 48 h treatment. data represent important step toward validation CPB target, well aiding new drug discovery studies based on protease.

Language: Английский

Citations

0