Novel camphor-based pyrimidine derivatives induced cancer cell death through a ROS-mediated mitochondrial apoptosis pathway

Zhang, Yan; Wang, Yunyun; Zhao, Yuxun; Gu, Wen; Zhu, Yongqiang; Wang, Shifa

doi:10.1039/c9ra05900h

Cited by 13 publications

(5 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, at the molecular level, an increase in the formation of apoptotic proteins Bax, cytochrome C, and caspase 3 was observed, although the formation of the anti-apoptotic protein Bcl-2 was significantly decreased. The proper anti-oncogenic effect was present in ROS accumulation in the cell and toxicity to mitochondria, which in turn induced the apoptosis pathway [ 94 ].…”

Section: Molecular Activity Of Camphormentioning

confidence: 99%

“…The preparation showed an MIC for E. coli at 8 μg/mL vs. 2 μg/mL for the positive control can, and 16 µg/mL for P. aeruginosa versus 32 µg/mL for ACN. Zhang et al also described significant activity of one of the compounds against MRSA isolates (MIC = 8 μg/mL vs. positive control CAN’s MIC = 1 μg/mL) and against pathogenic fungi C. albicans (MIC = 32 μg/mL vs. ketoconazole’s MIC = 16 μg/mL) [ 94 ].…”

Section: Antimicrobial Activity Of Camphormentioning

confidence: 99%

See 1 more Smart Citation

Is Camphor the Future in Supporting Therapy for Skin Infections?

Duda-Madej,

Viscardi,

Grabarczyk

et al. 2024

Pharmaceuticals

View full text Add to dashboard Cite

The aim of this review is to present the potential application of camphor—a bicyclic monoterpene ketone—in the prevention of skin infections. Skin diseases represent a heterogeneous group of disorders characterized by prolonged symptoms that significantly diminish the quality of life. They affect the dermis, the epidermis, and even subcutaneous tissue. They very often have a bacterial or fungal background. Therapy for dermatological skin disorders is difficult and long-term. Therefore, it is important to find a compound, preferably of natural origin, that (i) prevents the initiation of this infection and (ii) supports the skin’s repair process. Based on its documented anti-inflammatory, antibacterial, antifungal, anti-acne, anesthetic, strengthening, and warming properties, camphor can be used as a preventative measure in dermatological infectious diseases and as a component in medical and cosmetic products. This work discusses the structure and physicochemical properties of camphor, its occurrence, and methods of obtaining it from natural sources as well as through chemical synthesis. The use of camphor in industrial preparations is also presented. Additionally, after a detailed review of the literature, the metabolism of camphor, its interactions with other medicinal substances, and its antimicrobial properties against bacteria and fungi involved in skin diseases are discussed with regard to their resistance.

show abstract

Section: Molecular Activity Of Camphormentioning

confidence: 99%

Section: Antimicrobial Activity Of Camphormentioning

confidence: 99%

Is Camphor the Future in Supporting Therapy for Skin Infections?

Duda-Madej,

Viscardi,

Grabarczyk

et al. 2024

Pharmaceuticals

View full text Add to dashboard Cite

show abstract

“…A camphor-based pyrimidine has been reported to promote apoptosis associated with increased expression of pro-apoptotic proteins Bax, cytochrome C, and caspase-3 and decreased expression of anti-apoptosis protein Bcl-2 [25]. Herein, the effect of PC-12 on the expression of apoptotic genes and PARP cleavage (one of the hallmarks of apoptosis) was examined.…”

Section: Pc-12 Induces Cleavage Of Parp and Regulated The Expression ...mentioning

confidence: 99%

Discovery of Pyrimidine- and Coumarin-Linked Hybrid Molecules as Inducers of JNK Phosphorylation through ROS Generation in Breast Cancer Cells

Kim

Vishwanath

et al. 2023

Molecules

View full text Add to dashboard Cite

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer exhibits early relapses, poor prognoses, and high recurrence rates. Herein, a JNK-targeting compound has been developed that may be of utility in HER2-positive mammary carcinoma. The design of a pyrimidine-and coumarin-linked structure targeting JNK was explored and the lead structure PC-12 [4-(3-((2-((4-chlorobenzyl)thio) pyrimidin-4-yl)oxy)propoxy)-6-fluoro-2H-chromen-2-one (5d)] was observed to selectively inhibit the proliferation of HER2-positive BC cells. The compound PC-12 exerted DNA damage and induced apoptosis in HER-2 positive BC cells more significantly compared to HER-2 negative BC cells. PC-12 induced PARP cleavage and down-regulated the expression of IAP-1, BCL-2, SURVIVIN, and CYCLIN D1 in BC cells. In silico and theoretical calculations showed that PC-12 could interact with JNK, and in vitro studies demonstrated that it enhanced JNK phosphorylation through ROS generation. Overall, these findings will assist the discovery of new compounds targeting JNK for use in HER2-positive BC cells.

show abstract

“…The camphor derivatives exhibits numbers of pharmacological actions, for example, N‐arylpiperazine camphor sulfonamides were reported as novel chemokine receptor (CXCR3) antagonists. Based on the previous studies of camphor scaffold for anticancer activities, Zhang et al., (2019) synthesized and reported 24 novel camphor‐based pyrimidine derivatives. Synthesized compounds were evaluated for cytotoxic studies by MTS assay in MDA‐MB‐231, A‐549 and in RPMI‐8226 (multiple myeloma) cancer cells.…”

Section: Caspase‐3 Activatorsmentioning

confidence: 99%

Caspase‐3: A primary target for natural and synthetic compounds for cancer therapy

Yadav

Jain³

et al. 2021

Chem Biol Drug Des

100

View full text Add to dashboard Cite

Caspases, a group of protease enzymes (cysteine proteases), exist as inactive zymogens in the cells and execute apoptosis (programmed cell death). Caspase‐3, an executioner caspase, plays an imperative role in apoptosis and becomes a primary target for cancer treatment. A number of analogues of quinazoline, quinazolinone, indoloquinazolines, quinone, naphthoquinones, pyrroloiminoquinones, styrylquinolines, tetheredtetrahydroquinoline, fluoroquinolone, thiosemicarbazones, benzotriazole, pyrimidines, chalcone, and carbazoles have been reported till date, representing caspase‐3 mediated apoptosis for cancer therapy. Simultaneously, plant isolates, including lysicamine, podophyllotoxin, and majoranolide, have also been claimed for caspase‐3‐mediated apoptosis‐induced cytotoxicity. Procaspase‐activating compound‐1 (PAC‐1) is the first FDA approved orphan drug, and its synthetic derivative WF‐208 also showed fascinating caspase‐3 mediated anticancer activity. Till date, a large number of compounds have been reported and patented for their caspase‐3‐mediated cytotoxicity and now scientist is also focusing to introduce new compounds in market to encompass anticancer activity.

show abstract

Novel camphor-based pyrimidine derivatives induced cancer cell death through a ROS-mediated mitochondrial apoptosis pathway

Abstract: A series of novel camphor-based pyrimidine derivatives were synthesized and characterized. We found the compound 3f exhibited strongest anti-tumor activity via ROS-mediated mitochondrial apoptosis pathway.

Cited by 13 publications

References 42 publications

Is Camphor the Future in Supporting Therapy for Skin Infections?

Is Camphor the Future in Supporting Therapy for Skin Infections?

Discovery of Pyrimidine- and Coumarin-Linked Hybrid Molecules as Inducers of JNK Phosphorylation through ROS Generation in Breast Cancer Cells

Caspase‐3: A primary target for natural and synthetic compounds for cancer therapy

Contact Info

Product

Resources

About