Coumarin-1,2,3-triazole Hybrid Molecules: An Emerging Scaffold for Combating Drug Resistance DOI
Harish C. Upadhyay

Current Topics in Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 21(8), P. 737 - 752

Published: March 1, 2021

Undoubtedly, antibiotics have saved billions of lives, but lack novel antibiotics, development resistance mechanisms in almost all clinical isolates bacteria, and recurrent infections caused by persistent bacteria hamper the successful treatment infections. Due to widespread emergence resistance, even new families anti-microbial agents a short life expectancy. Drugs acting on single target often lead drug are associated with various side effects. For overcoming this problem, either multidrug therapy, or multiple targets may be used. The latter is called ‘hybrid molecules,’ which formed clubbing two biologically active pharmacophores together, without an appropriate linker. In rapidly evolving era, natural product-based hybrid molecules super-alternative for combating bacterial fungal strains. Coumarins (benzopyran-2-one) one earliest reported plant secondary metabolites having clinically proven diverse range pharmacological properties. On other hand, 1,2,3-triazole common pharmacophore many drugs responsible polar interactions, improving solubility binding affinity biomolecular targets. review, we discuss recent advances Coumarin-1,2,3-triazole hybrids as potential anti-bacterial agents, aiming provide useful platform exploration leads broader spectrum, more effectiveness less toxicity modes action cost-effective safer future.

Language: Английский

1,3,4-Oxadiazole-containing hybrids as potential anticancer agents: Recent developments, mechanism of action and structure-activity relationships DOI Creative Commons
Swarnagowri Nayak, Santosh L. Gaonkar,

Ebraheem Abdu Musad

et al.

Journal of Saudi Chemical Society, Journal Year: 2021, Volume and Issue: 25(8), P. 101284 - 101284

Published: June 19, 2021

Chemotherapy is an important therapeutic approach for the treatment of cancer. Currently, many anticancer drugs are available in market that plays role cancer treatment, but concerns such as, drug resistance and side effects create urgent need development new anti-tumor with high potency less effects. Heterocycles great interest due to their fascinating activity. Among them, 1,3,4-oxadiazoles showed attracting activity its derivatives under clinical trials Hybridization 1,3,4-oxadiazole moiety other heterocyclic pharmacophoresis a promising overcome various disadvantages current as resistance, toxicity, Thus, 1,3,4-oxadiazole-heterocycle hybrids occupy significant position discovery drugs. reported oxadiazole-based reviewed here, compounds 45i, 59j, 62x highest IC50 values nanomolar range. This review summarizes recent developments potential, structure–activity relationships, mechanisms actions hybrids.

Language: Английский

Citations

75
Electrospun Nanofibers of Polycaprolactone/Collagen as a Sustained-Release Drug Delivery System for Artemisinin DOI Creative Commons
Peipei Huo,

Xinxu Han,

W. Zhang

et al.

Pharmaceutics, Journal Year: 2021, Volume and Issue: 13(8), P. 1228 - 1228

Published: Aug. 9, 2021

The application of artemisinin (ART) in the treatment malaria has been restricted to a certain degree due its inherent limitations, such as short half-life, poor solubility, limited bioavailability, and re-crystallization. Electrospun nanofibers loaded with ART provide an excellent solution these limitations yield sustained drug release well inhibition In this study, ART-loaded polycaprolactone (PCL)/collagen (Col) different proportions polymers were prepared. PCL/Col characterized, further anti-crystallization behaviors studied. SEM was used observe morphology nanofibers. X-ray diffraction (XRD) characterize physical state Fourier transform infrared spectroscopy (FTIR), water contact angle measurement, weight loss, swelling, experiments can verify differences performance polymer ratios. curve analyzed by kinetics, showing for up 48 h, followed Fickian mechanism, which shown diffusion index value obtained from Korsmeyer-Peppas equation.

Language: Английский

Citations

71
Design, Synthesis, and Anti-Inflammatory Activity of Some Coumarin Schiff Base Derivatives: In silico and in vitro Study DOI Creative Commons
Shokhan Jamal Hamid, Twana Salih

Drug Design Development and Therapy, Journal Year: 2022, Volume and Issue: Volume 16, P. 2275 - 2288

Published: July 1, 2022

Inflammation is a fundamental response of the immune system during tissue damage or pathogen infection to protect and maintain homeostasis. However, inflammation may lead life-threatening conditions. The most common treatment non-steroidal anti-inflammatory drugs (NSAIDs). Nowadays, development safer new NSAIDs critical as existing have serious adverse effects, such gastrointestinal (GI) toxicity cardiotoxicity. In present study, four compounds Schiff base derivatives 7-hydroxy-4-formyl coumarin 7-methoxy-4-formyl were designed synthesized aiming develop compound that exhibits activity circumvents side effects NSAIDs, especially GI toxicity.Lipinski's rule five was applied for each molecule evaluate drug-likeness properties. Molecular docking studies performed using ligands cyclooxygenase-2 (COX-2) protein select best-scored AutoDock 4.2.6. molecules then characterized. An in vitro assay against COX-2 receptor realized through denaturation assay.All passed Lipinski's exhibited higher binding free energy compared positive standard control (ibuprofen), Ki values 5, 7, 8 nanomolar range. only 6 7 obtained percentage inhibition relative ibuprofen.The study suggested be because this ligand not best computational experimental results but also strongest correlation between concentration (R = 0.986 R2 0.972) with lowest P-value (0.014).

Language: Английский

Citations

53
Synthetic and natural coumarins as potent anticonvulsant agents: A review with structure–activity relationship DOI Open Access

Rangappa S. Keri,

Srinivasa Budagumpi,

Sasidhar B. Somappa

et al.

Journal of Clinical Pharmacy and Therapeutics, Journal Year: 2022, Volume and Issue: 47(7), P. 915 - 931

Published: March 15, 2022

What is known and objective The main of this review to highlight the most relevant studies since 1990 (to date) in area medicinal chemistry aspects provide a panoramic view biologists/medicinal chemists working would assist them their efforts design, synthesize extract (from natural source) coumarin-based anticonvulsant agents. Also, structure–activity relationship (SAR) are also discussed for further rational design kind derivatives. It hoped that will be helpful new thoughts quest designs more active less toxic antiepileptic Methods A literature emphasizing application coumarin core as agents identify articles related topic; we performed standardized search from November 2021, using engines like Scifinder, web Science, Pubmed Scopus. Results discussion This gives an overview attempts shed light compile published reports on derivatives along with some opinions different approaches help designing future generation potent yet safer possible relationships (SARs) indicate direction effective candidates. conclusion findings indications or directions discovery better drugs synthetic naturally occurring coumarins In our review, have tried depict recent researches which made development novel compounds nucleus. SAR expressed indicated choice fitting substitution containing electron-withdrawing/donating groups heterocyclic moieties joined parent skeleton assumes essential role changing activity synthesized These encourage scientific community towards optimization pharmacological profile structural moiety important scaffold treatment epilepsy.

Language: Английский

Citations

48
4-Thiazolidinone-Bearing Hybrid Molecules in Anticancer Drug Design DOI Open Access
Piotr Roszczenko, Serhii Holota, Olga Szewczyk‐Roszczenko

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 13135 - 13135

Published: Oct. 28, 2022

Oncological diseases have currently reached an epidemic scale, especially in industrialized countries. Such a situation has prompted complex studies medicinal chemistry focused on the research and development of novel effective anticancer drugs. In this review, data concerning new 4-thiazolidinone-bearing hybrid molecules with potential activity reported during period from years 2017–2022 are summarized. The main emphasis is application molecular hybridization methodologies strategies design small as agents. Based analyzed data, it was observed that directions field scaffolds, hybrid-pharmacophore approach, analogue-based drug 4-thiazolidinone cores early approved drugs, natural compounds, privileged heterocyclic scaffolds. mentioned approaches tools/sources for generation hit/lead compounds will be relevant to future studies.

Language: Английский

Citations

45
Natural Coumarin Derivatives Activating Nrf2 Signaling Pathway as Lead Compounds for the Design and Synthesis of Intestinal Anti-Inflammatory Drugs DOI Creative Commons
Luiz Cláudio Di Stasi

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(4), P. 511 - 511

Published: March 30, 2023

Nrf2 (nuclear factor erythroid 2-related 2) is a transcription related to stress response and cellular homeostasis that plays key role in maintaining the redox system. The imbalance of system triggering for initiation progression non-communicable diseases (NCDs), including Inflammatory Bowel Disease (IBD). its inhibitor Kelch-like ECH-associated protein 1 (Keap1) are main regulators oxidative their activation has been recognized as promising strategy treatment or prevention several acute chronic diseases. Moreover, Nrf2/keap signaling pathway promotes inhibition NF-κB, transcriptional pro-inflammatory cytokines expression, synchronically promoting an anti-inflammatory response. Several natural coumarins have reported potent antioxidant intestinal compounds, acting by different mechanisms, mainly modulator pathway. Based on vivo vitro studies, this review focuses obtained from both plant products fermentative processes food plants gut microbiota, which activate produce activity. Although metabolites urolithin A B well other plant-derived display activity modulating pathway, studies necessary better pharmacological characterization evaluation potential lead compounds. Esculetin, 4-methylesculetin, daphnetin, osthole, imperatorin most coumarin derivatives compounds design synthesis activators with However, further structure–activity relationships experimental models inflammation subsequent clinical trials health disease volunteers essential determine efficacy safety IBD patients.

Language: Английский

Citations

27
Synthesis and biological evaluation of coumarine-imidazo[1,2-c][1,2,3]triazoles: PEG-400 mediated one-pot reaction under ultrasonic irradiation DOI

Rajkumar Samala,

Satheesh Kumar Nukala, Ravinder Manchal

et al.

Journal of Molecular Structure, Journal Year: 2023, Volume and Issue: 1290, P. 135944 - 135944

Published: June 4, 2023

Language: Английский

Citations

22
Michael Acceptors as Anti-Cancer Compounds: Coincidence or Causality? DOI Open Access
Celia María Curieses Andrés, José Manuel Pérez de la Lastra, Elena Bustamante Munguira

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 6099 - 6099

Published: June 1, 2024

Michael acceptors represent a class of compounds with potential anti-cancer properties. They act by binding to nucleophilic sites in biological molecules, thereby disrupting cancer cell function and inducing death. This mode action, as well their ability be modified targeted, makes them promising avenue for advancing therapy. We are investigating the molecular mechanisms underlying interactions cells, particular interfere cellular processes induce apoptosis. The properties not accidental but due chemical structure reactivity. electrophilic nature these allows selectively target residues on disease-associated proteins, resulting significant therapeutic benefits minimal toxicity various diseases. opens up new perspectives development more effective precise drugs. Nevertheless, further studies essential fully understand impact our discoveries translate into clinical practice.

Language: Английский

Citations

13
A survey of isatin hybrids and their biological properties DOI Creative Commons

Vanessa Asoh Shu,

Donatus Bekindaka Eni, Fidele Ntie‐Kang

et al.

Molecular Diversity, Journal Year: 2024, Volume and Issue: unknown

Published: June 4, 2024

Abstract The emergence of diverse infections worldwide, which is a serious global threat to human existence, necessitates the urgent development novel therapeutic candidates that can combat these diseases with efficacy. Molecular hybridization has been established as an efficient technique in designing bioactive molecules capable fighting infections. Isatin, core nucleus array compounds biological properties be modified at different positions leading creation drug targets, active area medicinal chemistry. This review containing published articles from 2005 2022 highlights isatin hybrids have synthesized and reported literature alongside discussion on their properties. enriched structure–activity relationship studies discussed provides insights for rational design tailored effective inspired by nature.

Language: Английский

Citations

10
Electrophilic Compounds in the Human Diet and Their Role in the Induction of the Transcription Factor NRF2 DOI Open Access
Celia María Curieses Andrés, José Manuel Pérez de la Lastra, Elena Bustamante Munguira

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3521 - 3521

Published: March 20, 2024

The phrase “Let food be thy medicine…” means that can a form of medicine and food; in other words, the diet we eat have significant impact on our health well-being. Today, this is gaining prominence as more scientific evidence suggests one’s help prevent treat disease. A rich fruits, vegetables, whole grains, lean protein reduce risk heart disease, cancer, diabetes, problems and, hand, processed foods, added sugars, saturated fats increase same diseases. Electrophilic compounds health, they are molecules covalently modify cysteine residues present thiol-rich Keap1 protein. These bind to activate NRF2, which promotes its translocation nucleus binding DNA ARE region, triggering antioxidant response protecting against oxidative stress. include polyphenols flavonoids nucleophilic but converted electrophilic quinones by metabolic enzymes such polyphenol oxidases (PPOs) sulfur foods Brassica genus (broccoli, cauliflower, cabbage, Brussel sprouts, etc.) garlic. This review summarizes current knowledge subject.

Language: Английский

Citations

8