Current Drug Research Reviews - Volume 13, Issue 2, 2021

Naltrexone (NTX) is an opioid antagonist that inhibits cell proliferation in vivo when administered in low doses. Naltrexone in low doses can reduce tumor growth by interfering with cell signalling as well as by modifying the immune system. It acts as an Opioid Growth Factor receptor (OGFr) antagonist and the OGF-OGFr axis is an inhibitory biological pathway present in human cancer cells and tissues, being a target for the treatment with naltrexone low-dose (LDN). Clinical trials have proposed a unique mechanism(s) allowing LDN to affect tumors. LDN shows promising results for people with primary cancer of the bladder, breast, liver, lung, lymph nodes, colon and rectum. This short review provides further evidence to support the role of LDN as an anticancer agent.

Background: Oxadiazole core displays various pharmacological properties among five membered nitrogen heterocyclic compounds, specially 1,3,4-oxadiazole containing molecules that have occupied a particular place in the field of synthetic medicinal chemistry as surrogates (bioisosteres) of carboxylic acids, carboxamides and esters. Moreover, they are having widespread kind of applications in numerous zones as polymers, as luminescence producing materials and as electron- transporting materials and corrosion inhibitors. Methods: This study contains comprehensive and extensive literature survey on chemical reactivity and biological properties associated with 1,3,4-oxadiazole containing compounds. Results: This review summarises 1,3,4-oxadiazole moiety in numerous compounds with reported pharmacological activity such as antiviral, analgesic and anti-inflammatory, antitumor, antioxidant, insecticidal and anti-parasitic, etc. Nevertheless, ring opening reactions of the 1,3,4-oxadiazole core have also made great attention, as they produce new analogues containing an aliphatic nitrogen atom and to other ring systems. Conclusion: In relation to the occurrence of oxadiazoles in biologically active molecules, 1,3,4- oxadiazole core emerges as a structural subunit of countless significance and usefulness for the development of new drug aspirants applicable to the treatment of many diseases. It concludes that 1,3,4-oxadiazole core compounds are more efficacious and less toxic medicinal agents with respect to new opinions in the search for rational strategies.

Drug repositioning or repurposing is a revolutionary breakthrough in drug development that focuses on rediscovering new uses for old therapeutic agents. Drug repositioning can be defined more precisely as the process of exploring new indications for an already approved drug while drug repurposing includes overall re-development approaches grounded in the identical chemical structure of the active drug moiety as in the original product. The repositioning approach accelerates the drug development process, curtails the cost and risk inherent to drug development. The strategy focuses on the polypharmacology of drugs to unlocks novel opportunities for logically designing more efficient therapeutic agents for unmet medical disorders. Drug repositioning also expresses certain regulatory challenges that hamper its further utilization. The review outlines the eminent role of drug repositioning in new drug discovery, methods to predict the molecular targets of a drug molecule, advantages that the strategy offers to the pharmaceutical industries, explaining how the industrial collaborations with academics can assist in the discovering more repositioning opportunities. The focus of the review is to highlight the latest applications of drug repositioning in various disorders. The review also includes a comparison of old and new therapeutic uses of repurposed drugs, assessing their novel mechanisms of action and pharmacological effects in the management of various disorders. Various restrictions and challenges that repurposed drugs come across during their development and regulatory phases are also highlighted.

Infectious diseases have been prevalent for many decades and viral pathogens have caused global health crises and economic meltdown on a devastating scale. The high occurrence of novel viral infections in recent years, in spite of the progress achieved in the field of pharmaceutical sciences, defines the critical need for newer and more effective antiviral therapies and diagnostics. The incidence of multi-drug resistance and adverse effects due to the prolonged use of anti-viral therapy is also a major concern. Nanotechnology offers a cutting edge platform for the development of novel compounds and formulations for biomedical applications. The unique properties of nano-based materials can be attributed to the multi-fold increase in the surface to volume ratio at the nano-scale, tunable surface properties of charge and chemical moieties. Idealistic pharmaceutical properties such as increased bioavailability and retention times, lower toxicity profiles, sustained- release formulations, lower dosage forms and most importantly, targeted drug delivery can be achieved through the approach of nanotechnology. The extensively researched nano-based materials are metal and polymeric nanoparticles, dendrimers and micelles, nano-drug delivery vesicles, liposomes and lipid-based nanoparticles. In this review article, the impact of nanotechnology on the treatment of Human Immunodeficiency Virus (HIV) and Herpes Simplex Virus (HSV) viral infections during the last decade is outlined.

Rheumatoid arthritis not only affects synovial joints but also many other sites including heart, blood vessels, and skins. It is more common in females than in males. The exact cause of rheumatoid arthritis is not well established, but the hypothesis reported in the literature is that in the development stage of the disease, both genetics and environmental factors can play an inciting role. Along with these factors, the alteration in the normal physiology of enzymatic action acts as a trigger to develop this condition. Numerous signaling pathways in the pathogenesis of Rheumatoid Arthritis involve activation of mitogen-activated protein kinase, kinases Janus family, P-38 Mitogen- Activated Protein Kinase and Nuclear Factor-kappa B. Interleukin-1, is a proinflammatory cytokine that plays an important role in inflammation in RA. These are also associated with an increase in neutrophil, macrophage and lymphocytic chemotaxis, mast cell degranulation, activation, maturation and survival of T-cells and B-cells activated. These signaling pathways also show that p38α downregulation in myeloid cells exacerbates the severity of symptoms of arthritis. Thus, the present review carters about the detail of different signaling pathways and their role in rheumatoid arthritis.

Sirtuins are NAD+ dependent enzymes that have a predominant role in neurodegenerative disorders and also regulate the inflammatory process, protein aggregation, etc. The relationships between sirtuins with that of the nervous system and neurodegeneration, are widely studied. Sirtuins have a strong role in metabolic syndrome in mitochondria also. The activities of sirtuins can be altered by using small molecules that would be developed into drugs and it is proven that the manipulation of SIRT1 activity influences neurodegenerative disease models. They are interesting since using small molecules, which would be developed into a drug, it is feasible to alter the activities of sirtuins. Different functions of sirtuins depend upon their subcellular localization. In this review paper, we discuss different sirtuins, differential expression of sirtuins, and expression of sirtuin in the brain and briefly explains Sirtuin3 (SIRT3).

Aim: The aim of this study was to determine the proliferation of MCF-7 following irradiation or hyperthermia as alone or pre-treatment with suberosin.

Background: Radiotherapy is a major therapeutic modality for the control of breast cancer. However, hyperthermia can be prescribed for relief of pain or enhancing cancer cell death. Some studies have attempted its use as an adjuvant to improve therapeutic efficiency. Suberosin is a cumarin- derived natural agent that has shown anti-inflammatory properties.

Objective: In this in vitro study, possible sensitization effect of suberosin in combination with radiation or hyperthermia was evaluated.

Methods: MCF-7 breast cancer cells were irradiated or received hyperthermia with or without treatment with suberosin. The incidence of apoptosis as well as viability of MCF-7 cells were observed. Furthermore, the expressions of pro-apoptotic genes such as Bax, Bcl-2, and some caspases were evaluated using real-time PCR.

Results: Both radiotherapy or hyperthermia reduced the proliferation of MCF-7 cells. Suberosin amplified the effects of radiotherapy or hyperthermia for induction of pro-apoptotic genes and reducing cell viability.

Conclusion: Suberosin has a potent anti-cancer effect when combined with radiotherapy or hyperthermia. It could be a potential candidate for killing breast cancer cells as well as increasing the therapeutic efficiency of radiotherapy or hyperthermia.

Background: Pharmacotherapy for Alcohol Dependence (AD) is underutilized. Barriers preventing the use of AD medications include high prices, lack of access to prescribing physicians, and a limited number of available medications. Objective: The study evaluated the use of AD medications in a sample of Italian outpatients who received these medications free of charge, had access to physicians during office hours, and for whom substitution therapy [gamma-hydroxybutyrate (GHB)] was available. We also evaluated the rate of patients who received a combination of non-pharmacological and pharmacological treatments among participants who were still drinking. Methods: SCID for AD and questionnaire were filled by to AD outpatients during a face-to-face interview. Results & Discussion: 345 AD outpatients were interviewed: 58.8% were currently receiving at least one AD medication (GHB: 34.3%, disulfiram: 29.6%, acamprosate: 5.9%; naltrexone: 2.5%; more than one medication: 16.7%). Less than 30% of participants who were still drinking, received a combination of non-pharmacological and pharmacological treatments. Nonetheless, we found higher use of AD medications compared to previous studies conducted in other countries. This higher use of AD medications may be due to access to free medications, prescribing physicians’ style, and a larger number of available medications. Conclusion: Our results confirm the underutilization of AD medications, as less than 60% of AD outpatients received medications, and less than 30% of those who were still drinking, received a combination of non-pharmacological and pharmacological treatments. These findings may be useful in improving our knowledge of the barriers that prevent the use of AD medications in clinical practice.