Current Pharmaceutical Design - Volume 27, Issue 1, 2021

Curcumin is a major curcuminoid present in turmeric. The compound is attributed to various therapeutic properties, which include anti-oxidant, anti-inflammatory, anti-bacterial, anti-malarial, and neuroprotection. Due to its therapeutic potential, curcumin has been employed for centuries in treating different ailments. Curcumin has been investigated lately as a novel therapeutic agent in the treatment of cancer. However, the mechanisms by which curcumin exerts its cytotoxic effects on malignant cells are still not fully understood. One of the main limiting factors in the clinical use of curcumin is its poor bioavailability and rapid elimination. Advancements in drug delivery systems such as nanoparticle-based vesicular drug delivery platforms have improved several parameters, namely, drug bioavailability, solubility, stability, and controlled release properties. The use of curcumin-encapsulated niosomes to improve the physical and pharmacokinetic properties of curcumin is one such approach. This review provides an up-to-date summary of nanoparticle-based vesicular drug carriers and their therapeutic applications. Specifically, we focus on niosomes as novel drug delivery formulations and their potential in improving the delivery of challenging small molecules, including curcumin. Overall, the applications of such carriers will provide a new direction for novel pharmaceutical drug delivery, as well as for biotechnology, nutraceutical, and functional food industries.

Since the discovery of DNA intercalating agents (by Lerman, 1961), a growing number of organic, inorganic, and metallic compounds have been developed to treat life-threatening microbial infections and cancers. Fused-heterocycles are amongst the most important group of compounds that have the ability to interact with DNA. DNA intercalators possess a planar aromatic ring structure that inserts itself between the base pairs of nucleic acids. Once inserted, the aromatic structure makes van der Waals interactions and hydrogen-bonding interactions with the base pairs. The DNA intercalator may also contain an ionizable group that can form ionic interactions with the negatively charged phosphate backbone. After the intercalation, other cellular processes could take place, leading ultimately to cell death. The heterocyclic nucleus present in the DNA intercalators can be considered as a pharmacophore that plays an instrumental role in dictating the affinity and selectivity exhibited by these compounds. In this work, we have carried out a revision of small organic molecules that bind to the DNA molecule via intercalation and cleaving and exert their antitumor activity. A general overview of the most recent results in this area, paying particular attention to compounds that are currently under clinical trials, is provided. Advancement in spectroscopic techniques studying DNA interaction can be examined in-depth, yielding important information on structure-activity relationships. In this comprehensive review, we have focused on the introduction to fused heterocyclic agents with DNA interacting features, from medicinal point of view. The structure-activity relationships points, cytotoxicity data, and binding data and future perspectives of medicinal compounds have been discussed in detail.

Background: An endo-β-glucuronidase enzyme, Heparanase (HPSE), degrades the side chains of polymeric heparan sulfate (HS), a glycosaminoglycan formed by alternate repetitive units of D-glucosamine and D-glucuronic acid/L-iduronic acid. HS is a major component of the extracellular matrix and basement membranes and has been implicated in processes of the tissue’s integrity and functional state. The degradation of HS by HPSE enzyme leads to conditions like inflammation, angiogenesis, and metastasis. An elevated HPSE expression with a poor prognosis and its multiple roles in tumor growth and metastasis has attracted significant interest for its inhibition as a potential anti-neoplastic target. Methods: We reviewed the literature from journal publication websites and electronic databases such as Bentham, Science Direct, PubMed, Scopus, USFDA, etc., about HPSE, its structure, functions, and role in cancer. Results: The present review is focused on Heparanase inhibitors (HPIns) that have been isolated from natural resources or chemically synthesized as new therapeutics for metastatic tumors and chronic inflammatory diseases in recent years. The recent developments made in the HPSE structure and function are also discussed, which can lead to the future design of HPIns with more potency and specificity for the target. Conclusion: HPIns can be a better target to be explored against various cancers.

Background: Infectious diseases constantly represent the source of sickness as well as mortality in human beings. Herbal applications in human life through using plants for antibacterial and anticancer activity have shown the potential medicinal outcome. Objectives: To evaluate the antibacterial and anticancer activities of the crude extract of Matricaria aurea. Materials and Methods: The antibacterial activity of the crude flowers of M. aurea extract was examined against reference and clinical bacterial strains by agar well diffusion method. Minimum inhibitory concentrations and minimum bactericidal concentrations were determined by micro broth dilution assays using MH broth. Herbal extract was employed over human breast adenocarcinoma cell line (MCF-7), hepatocellular carcinoma cell line (HepG-2) and colorectal adenocarcinoma cell line (HCT-116) to optimize cancer cells proliferation by SRB assay. Results: The data has shown that the extract from M. aurea had significant antimicrobial activity against the tested microorganisms. The plant extract showed higher antibacterial activity against the reference strain of Streptococcus pyogenes. The MIC and MBC varied between 0.38-12.5 mg/ml and 3.1-200 mg/ml respectively. Synergy study elucidated the significant bacteriostatic effect of M. aurea extract on S. aureus and S. saprophyticus. The data of SRB assay deliver the potential anticancer activity through cell death. Conclusion: This study delivers innovative information that M. aurea possessed excellent bio-activities against pathogenic microbes and cancer cells, which drive attention for further research to explore the active components responsible for biological efficacies.

Ischemic heart disease is the main cause of death globally. In the heart, the ischemia/reperfusion injury gives rise to a complex cascade of molecular signals, called cardiac remodeling, which generates harmful consequences for the contractile function of the myocardium and consequently heart failure. Metformin is the drug of choice in the treatment of type 2 diabetes mellitus. Clinical data suggest the direct effects of this drug on cardiac metabolism and studies in animal models showed that metformin activates the classical pathway of AMP-activated protein kinase (AMPK), generating cardioprotective effects during cardiac remodeling, hypertrophy and fibrosis. Furthermore, new studies have emerged about other targets of metformin with a potential role in cardioprotection. This state of the art review shows the available scientific evidence of the cardioprotective potential of metformin and its possible effects beyond AMPK. Targeting of autophagy, mitochondrial function and miRNAs are also explored as cardioprotective approaches along with a therapeutic potential. Further advances related to the biological effects of metformin and cardioprotective approaches may provide new therapies to protect the heart and prevent cardiac remodeling and heart failure.

Background: Osteoporosis (OP) is the most common bone disease, which is listed by the World Health Organization (WHO) as the third major threat to life and health among the elderly. The etiology of OP is multifactorial, and its potential regulatory mechanism remains unclear. Long non-coding RNAs (LncRNAs) are the non-coding RNAs that are over 200 bases in the chain length. Increasing evidence indicates that LncRNAs are the important regulators of osteogenic and adipogenic differentiation, and the occurrence of OP is greatly related to the dysregulation of the bone marrow mesenchymal stem cells (BMSCs) differentiation lineage. Meanwhile, LncRNAs affect the occurrence and development of OP by regulating OP-related biological processes. Methods: In the review, we summarized and analyzed the latest findings of LncRNAs in the pathogenesis, diagnosis and related biological processes of OP. Relevant studies published in the last five years were retrieved and selected from the PubMed database using the keywords of LncRNA and OP. Results/Conclusion: The present study aimed to examine the underlying mechanisms and biological roles of LncRNAs in OP, as well as osteogenic and adipogenic differentiation. Our results contributed to providing new clues for the epigenetic regulation of OP, making LncRNAs the new targets for OP therapy.

Nanoshuttles are unique structures that resemble double-headed arrows or a nanorod with sharp tips for better penetration into the tumor cells, reduction of toxicity and minimization of off-targeting effect. These biologically- inspired multimetallic or bimetallic nano swimmers are capable of transporting cargoes from one end to another via self-propulsion in an efficient manner. Encapsulation with pH- and heat-sensitive polymers allows nanoshuttles to release cargos at the targeted site in a controlled fashion. This review article focuses on the methods of preparation and characterization of nanoshuttles with applications in the field of antineoplastic, antibacterial, erectile dysfunction, electrochemical biosensing, anticounterfeiting, on-demand and targeted delivery system for imaging as well as cell ablation therapy. Magnetic nanoshuttles exhibit modified optical properties for utilization in diagnostic imaging for sensitive and early diagnosis of diseases. Smart drug delivery is achieved when nanoshuttles are combined with nanomotors to exhibit distinctive, rapid and unidirectional movement in the bloodstream. Cost-effective synthesis of nanoshuttles will extend their applications in the commercial sectors by overcoming the limitations like scale-up and regulatory approval. In the near future, nanoshuttles will diversify in the fields of energy conversion, energy storage, 3D printing, stem cell fabrication and theranostics.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed coronavirus disease 2019 (COVID-19) by the World Health Organization, is a newly emerging zoonotic agent that emerged in China in December 2019. No specific treatment for COVID-19 is currently available. Usual palliative treatment includes maintaining hydration and nutrition and controlling fever and cough. The clinical severity and extent of transmission need to be determined, and therapeutic options need to be developed and optimized. Methods: The present review discusses the recent repurposing of drugs for COVID-19 treatment. Results: Several compounds, including remdesivir, lopinavir, ritonavir, interferon-β, ribavirin, chloroquine/ hydroxychloroquine, azithromycin, tocilizumab, and ivermectin, have emerged as promising alternatives. They block the virus from entering host cells, prevent viral replication, and attenuate exacerbation of the host's immune response. Conclusion: Although some evidence indicates the positive actions of different classes of compounds for the treatment of COVID-19, few clinical assays have been established to definitively demonstrate their therapeutic value in humans. Multicenter clinical studies are urgently needed to validate and standardize therapeutic regimens that involve these agents. Although science has not yet presented us with a specific drug against COVID-19, the repurposing of drugs appears to be promising in our fight against this devastating disease.

Background: CASC15, one of long non-coding RNA, is involved in the regulation of many tumor biological processes, and is expected to become a new biological therapeutic target. This paper aims to elucidate the pathophysiological function of CASC15 in various tumors. Methods: The relationship between CASC15 and tumors was analyzed by searching references, and summarized the specific pathophysiological mechanism of CASC15. Results: LncRNA CASC15 is closely related to tumor development, and has been shown to be abnormally high expressed in all kinds of tumors, including breast cancer, cervical cancer, lung cancer, hepatocellular carcinoma, gastric cancer, bladder cancer, colon cancer, colorectal cancer, cardiac hypertrophy, intrahepatic cholangiocarcinoma, leukemia, melanoma, tongue squamous cell carcinoma and nasopharyngeal carcinoma. However, CASC15 has been found to be down-expressed abnormally in ovarian cancer, glioma and neuroblastoma. Besides, it is identified that CASC15 can affect the proliferation, invasion and apoptosis of tumors. Conclusion: LncRNA CASC15 has the potential to become a new therapeutic target or marker for a variety of tumors.

Background: Pulmonary infections are an increasing problem in individuals and current therapies are lacking. Liposomes are spherical lipidic vesicles composed of phospholipid and cholesterol. Liposomes have numerous advantages, such as biodegradability, biocompatibility, non-immunogenicity, lack of toxicity, controlled release properties and high stability. Objective: This work was carried out to construct a novel liposomal moxifloxacin formulation and examine its antimicrobial effects against Pseudomonas aeruginosa and Staphylococcus aureus. Methods: The liposomal moxifloxacin formulation was prepared by the thin-film hydration method. The bilayer was composed of cholesterol and phospholipid at 30:70 molar ratio. To prepare cationic liposomes, 5% cationic agent (CTAB) was added. The liposomes were reduced in size with the bath sonication technique. The liposomal characterizations were tested regarding vesicle size, surface charge and drug encapsulation efficacy. Microdilution method was used to determine the Minimum Inhibitory Concentration (MIC) against Pseudomonas aeruginosa and Staphylococcus aureus of the free drug, neutral and cationic moxifloxacin liposomes. Results: The size of the liposomes was 50-70 nm. The zeta potential of neutral and cationic vesicles was ∼0 and +22 mV. The MIC values against Pseudomonas aeruginosa of the free drug, neutral and cationic moxifloxacin liposomes were 10, 5 and 2.5, respectively. The MICs against Staphylococcus aureus of the free drug, neutral and cationic moxifloxacin liposomes were 1, 1 and 0.5, respectively. Conclusion: This study demonstrates that the encapsulation of moxifloxacin into liposomes (especially cationic vesicles) could enhance antimicrobial properties.