Current Medicinal Chemistry - Volume 29, Issue 26, 2022

Cervical cancer is the fourth leading cause of cancer death among women worldwide. Due to cervical cancer's high incidence and mortality, there is an unmet demand for effective diagnostic, therapeutic, and preventive agents. At present, the preferred treatment strategies for advanced metastatic cervical cancer include surgery, radiotherapy, and chemotherapy. However, cervical cancer is gradually developing resistance to chemotherapy, thereby reducing its efficacy. Over the last several decades, phytochemicals, a general term for compounds produced from plants, have gained attention for their role in preventing cervical cancer. This role in cervical cancer prevention has garnered attention on the medicinal properties of fruits and vegetables. Phytochemicals are currently being evaluated for their ability to block proteins involved in carcinogenesis and chemoresistance against cervical cancer. Chemoresistance to cancer drugs like cisplatin, doxorubicin, and 5-fluorouracil has become a significant limitation of drug-based chemotherapy. However, the combination of cisplatin with other phytochemicals has been identified as a promising alternative to subjugate cisplatin resistance. Phytochemicals are promising chemo-preventive and chemotherapeutic agents as they possess antioxidant, anti-inflammatory, and anti-proliferative potential against many cancers, including cervical cancer. Furthermore, the ability of the phytochemicals to modulate cellular signaling pathways through up and down regulation of various proteins has been claimed for their therapeutic potential. Phytochemicals also display a wide range of biological functions, including cell cycle arrest, apoptosis induction, inhibition of invasion, and migration in cervical cancer cells. Numerous studies have revealed the critical role of different signaling proteins and their signaling pathways in the pathogenesis of cervical cancer. Here, we review the ability of several dietary phytochemicals to alter carcinogenesis by modulating various molecular targets.

The most typical malignant brain tumor, glioblastoma multiforme (GBM), seems to have a grim outcome, despite the intensive multi-modality interventions. Literature suggests that biologically active phytomolecules may exert anticancer properties by regulating several signaling pathways. Berberine, an isoquinoline alkaloid, has various pharmacological applications to combat severe diseases like cancer. Mechanistically, it inhibits cell proliferation and invasion, suppresses tumor angiogenesis, and induces cell apoptosis. The antitumoral effect of berberine in GBM is increasingly recognized. This review sheds new light on the regulatory signaling mechanisms of berberine in various cancers, proposing its potential role as a therapeutic agent for GBM.

Nanotechnology is a pioneer field of study for engineering smart nanosystems in targeted diagnosis and treatment in cancer therapy. Effective treatment for various types of solid tumors should ideally target malignant cells and tissue while having no effect on healthy cells in the body. Nano-sized graphene oxide (GO) and reduced graphene oxide (rGO) have phenomenal chemical versatility, high surface area ratio, and supernatural physical properties. The synergistic effects caused by the well-defined assembly of GO and rGO surface generate not only essential optical, mechanical, but also electronic behaviors. In multimodal cancer therapy, developing innovative multifunctional hybrid nanoparticles with significant potential is extensively considered. GO and rGO are programmable targeted delivery systems infused with photonic energy that may be used in photothermal treatment. Its remarkable properties indicated its applications as a biosensor, bio-imaging for cancer diagnosis. In this current review, we show a remarkable highlight about GO, rGO, and discuss the notable applications for cancer diagnosis and treatment, and provide an overview of possible cellular signaling pathways that are affected by GO, rGO in cancer treatment.

Leishmaniasis, a cutaneous, mucocutaneous, or visceral parasitic disease caused by the protozoa of the genus Leishmania, is responsible for approximately 20-40 thousand deaths annually, with Brazil, India, and certain countries in Africa being the most affected. In addition to the parasite’s ability to evade the host’s immune system, the incidence of vectors, genetics of different hosts, and several deaths are attributed to the limited conventional treatments that have high toxicity, low effectiveness, and prolonged therapeutic regimens. Thus, the development of new alternative therapeutic strategies remains warranted. Metallic nanoparticles, such as gold, silver, zinc oxide, and titanium dioxide, have shown promising therapeutic tools since they are easily prepared and chemically modified, have a broad spectrum of action and low toxicity, and can generate reactive oxygen species and other immune responses. This review explores the progress of the use of metallic nanoparticles as new tools in the treatment of leishmaniasis and discusses the gaps in knowledge hindering the development of a safe and effective therapeutic intervention against these infections.

Cancer is the world's second-largest cause of death. The most common cancer treatments are surgery, radiation therapy, and chemotherapy. Drug resistance, epithelial-- to-mesenchymal transition (EMT), and metastasis are pressing issues in cancer therapy today. Increasing evidence showed that drug resistance and EMT are co-related with each other. Indeed, drug-resistant cancer cells possess enhanced EMT and invasive ability. Recent research has demonstrated that lncRNAs (long non-coding RNAs) are non-coding transcripts which play an important role in the regulation of EMT, metastasis, and drug resistance in different cancers. However, the relationships among lncRNAs, EMT, and drug resistance are still unclear. These effects could be exerted via several signaling pathways, such as TGF-β, PI3K-AKT, and Wnt/β-catenin. Identifying the crucial regulatory roles of lncRNAs in these pathways and processes leads to the development of novel targeted therapies. We review the key aspects of lncRNAs associated with EMT and therapy resistance. We focus on the crosstalk between lncRNAs and molecular signaling pathways affecting EMT and drug resistance. Moreover, each of the mentioned lncRNAs could be used as a potential diagnostic, prognostic, and therapeutic therapy resistancefor cancer. However, the investigation of lncRNAs for clinical applications still has several challenges.

Pentamidine, an FDA-approved human drug for many protozoal infections, was initially synthesized in the late 1930s and first reported to be curative for parasitosis in the 1940s. After ninety years of sometimes quiet growth, pentamidine and its derivatives have gone far beyond antibacterial agents, including but not limited to the ligands of DNA minor groove, modulators of PPIs (protein-protein interactions) of the transmembrane domain 5 of lateral membrane protein 1, and the blockers of the SARS-CoV-2 3a channel. This mini-review highlights the development and applications of pentamidine and its analogs, aiming to provide insights for further developing pentamidine derivatives in the following decades.

Background: Viral resistance to existing inhibitors and the time-dependent effectiveness of neuraminidase inhibitors have limited the number of antivirals that can be used for prophylaxis and therapeutic treatment of severe influenza infection. Thus, there is an urgent need to develop new drugs to prevent and treat influenza infection. Objective: The aims of this study was to design and synthesize a novel series of 2-ureidonicotinamide derivatives and evaluate their anti-IAV activities. Furthermore, we predicted the abilities of these compounds to inhibit the PA-PB1 subunit and forecasted the docking poses of these compounds with RNA polymerase protein (PDB ID 3CM8). Methods: The novel designed compounds were synthesized using classical methods of organic chemistry and tested in vitro for their abilities inhibiting RNP and against influenza A virus. In addition, the 23 synthesized molecules were subjected to the generated pharmacophore Hypo1 to forecast the activity target PA-PB1 subunit of RNA polymerase. The ADMET pharmacokinetic parameters were calculated by the ADMET modules in Discovery Studio 2016. The docking results helped us demonstrate the possible interactions between these compounds with 3CM8. Results: The synthesized 2-ureidonicotinamide derivatives were characterized as potent anti-influenza inhibitors. The target compounds 7b and 7c demonstrated significant antiviral activities and could be considered as novel lead compounds of antiviral inhibitors. In addition, compound 7b revealed suitable ADME properties expressed and might be a significant RNA polymerase inhibitor targeting the PA-PB1 subunit based on the predictable results and the docking results. Conclusion: This study revealed a novel series of compounds that might be useful in the search for an effective drug against the influenza virus.