Auranofin and its analogs as prospective agents for the treatment of colorectal cancer

Today colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. This disease is poorly chemo-sensitive toward the existing medical treatments so that new and more effective therapeutic agents are urgently needed and intensely sought. Platinum drugs, oxaliplatin in particular, were reported to produce some significant benefit in CRC treatment, triggering the general interest of medicinal chemists and oncologists for metal-based compounds as candidate anti-CRC drugs. Within this frame, gold compounds and, specifically, the established antiarthritic drug auranofin with its analogs, form a novel group of promising anticancer agents. Owing to its innovative mechanism of action and its favorable pharmacological profile, auranofin together with its derivatives are proposed here as novel experimental agents for CRC treatment, capable of overcoming resistance to platinum drugs. Some encouraging results in this direction have already been obtained. A few recent studies demonstrate that the action of auranofin may be further potentiated through the preparation of suitable pharmaceutical formulations capable of protecting the gold pharmacophore from unselective reactivity or through the design of highly synergic drug combinations. The perspectives of the research in this field are outlined.

Insights into Structural Modifications of Valproic Acid and Their Pharmacological Profile

Valproic acid (VPA) is a well-established anticonvulsant drug discovered serendipitously and marketed for the treatment of epilepsy, migraine, bipolar disorder and neuropathic pain. Apart from this, VPA has potential therapeutic applications in other central nervous system (CNS) disorders and in various cancer types. Since the discovery of its anticonvulsant activity, substantial efforts have been made to develop structural analogues and derivatives in an attempt to increase potency and decrease adverse side effects, the most significant being teratogenicity and hepatotoxicity. Most of these compounds have shown reduced toxicity with improved potency. The simple structure of VPA offers a great advantage to its modification. This review briefly discusses the pharmacology and molecular targets of VPA. The article then elaborates on the structural modifications in VPA including amide-derivatives, acid and cyclic analogues, urea derivatives and pro-drugs, and compares their pharmacological profile with that of the parent molecule. The current challenges for the clinical use of these derivatives are also discussed. The review is expected to provide necessary knowledgebase for the further development of VPA-derived compounds.

Evaluation of Trans-Resveratrol as a Treatment for Periodontitis

Periodontitis is a globally prevalent inflammation-mediated disease that can result in varying degrees of destruction to the tissues supporting the teeth. The microbial pathogenic dysbiosis, oxidative stress, and deregulated inflammation, found in patients with periodontitis, make it a multifaceted condition that is difficult to fully resolve. Further to this, periodontitis has been associated with other systemic inflammatory conditions. Trans-resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a plant-derived molecule present in many foods, which have been shown to exhibit antimicrobial, antioxidant, anti-inflammatory, and regenerative properties. However, trans-resveratrol has been reported to have physicochemical shortcomings, which make its clinical translation a challenge. This review outlines a critical analysis of identified samples from the scientific literature that was conducted to assess the potential of RES as a viable therapeutic for periodontitis. The potential for the improvement of the limiting pharmacological profile of trans-resveratrol via nanoformulation is also explored.

Pharmacological profile of ficus thonningii: a review

Ficus thonningii is an African ethnomedicine plant used to treat a number of diseases. The nutritional, phytochemical, and pharmacological aspects of F. thonningii in relation to its therapeutic purposes are numerous. Ficus thonningii contains alkaloids, terpenoids, flavonoids, tannins, active proteins, and active proteins. Continue to identify, isolate, and quantify the active ingredients, as well as their medicinal purposes. Chronic toxicity, toxicology, antineoplastic effects, acute toxicity, hypoglycemic effects, antidiarrheal effects, analgesic effects, anti-inflammatory effects, antioxidants, antifungal activity, antimicrobial effects, antiprotozoal properties etc.

Phytochemicals against COVID -19, Pharmacological Perspectives: A Systematic Review

Background: Many publications discussed the potential role of medicinal plants in the management of COVID-19. However, clinical studies of the efficacy and safety of specified phytochemical(s) are limited. Objectives: To explore the pharmacological profile of specified compounds against COVID-19 Method: Systematic literature search of academic databases to explore specified phytochemicals for the management of COVID-19 using appropriate search terms. Rayyan software was used to organize 786 citations of which. 236 articles were included in this review. Results: Initially 70 compounds were identified to have a potential role in the management of COVID-19. In this review, 18 compounds were selected for further search Conclusion: In vitro anti-SARS-CoV-2activity has been demonstrated for a variety of natural compounds. However, preclinical research for most phytochemicals is scarce, and only a few compounds have been evaluated in clinical trials against COVID-19. A comprehensive pharmacological profile of these phytochemicals is urgently needed.

Effect of S–Se Bioisosteric Exchange on Affinity and Intrinsic Efficacy of Novel N-acylhydrazone Derivatives at the Adenosine A2A Receptor

In this work, we evaluated the conformational effect promoted by the isosteric exchange of sulfur by selenium in the heteroaromatic ring of new N-acylhydrazone (NAH) derivatives (3–8, 13, 14), analogues of the cardioactive compounds LASSBio-294 (1) and LASSBio-785 (2). NMR spectra analysis demonstrated a chemical shift variation of the iminic Csp2 of NAH S/Se-isosters, suggesting a stronger intramolecular chalcogen interaction for Se-derivatives. To investigate the pharmacological profile of these compounds at the adenosine A2A receptor (A2AR), we performed a previously validated functional binding assay. As expected for bioisosteres, the isosteric-S/Se replacement affected neither the affinity nor the intrinsic efficacy of our NAH derivatives (1–8). However, the N-methylated compounds (2, 6–8) presented a weak partial agonist profile at A2AR, contrary to the non-methylated counterparts (1, 3–5), which appeared as weak inverse agonists. Additionally, retroisosterism between aromatic rings of NAH on S/Se-isosters mimicked the effect of the N-methylation on intrinsic efficacy at A2AR, while meta-substitution in the phenyl ring of the acyl moiety did not. This study showed that the conformational effect of NAH-N-methylation and aromatic rings retroisosterism changed the intrinsic efficacy on A2AR, indicating the S/Se-chalcogen effect to drive the conformational behavior of this series of NAH.