Mini Reviews in Medicinal Chemistry - Volume 22, Issue 2, 2022

Abstract: Cancer is a frightful disease that still poses a 'nightmare' worldwide, causing millions of casualties annually imposing one of the human race's greatest health-care challenges that entail a pragmatic treatment strategy. Plants are repositories for new chemical entities and have a promising cancer research path, supplying 60% of the anticancer agents currently used. However, plants and plant-derived products revolutionize the field, as they are quick, cleaner, eco-friendly, low-cost, effective, and less toxic than conventional treatment methods. Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery and development. However, some alkaloids derived from natural herbs display anti-proliferation and antimetastatic activity on different forms of cancer both in vitro and in vivo. Alkaloids have also been widely formulated as anticancer medications, such as camptothecin and vinblastine. Based on the information in the literature, this review focuses on the naturally-derived bioactive alkaloids with prospective anticancer properties. Still, more research and clinical trials are required before final recommendations can be made on specific alkaloids.

Abstract: Severe Acute Respiratory Syndrome (SARS) is caused by different SARS viruses. In 2020, novel coronavirus (SARS-CoV-2) led to an ongoing pandemic, known as “Coronavirus Disease 2019 (COVID-19)”. The disease can spread among individuals through direct (via saliva, respiratory secretions, or secretion droplets) or indirect (through contaminated objects or surfaces) contact. The pandemic has spread rapidly from Asia to Europe and later to America. It continues to affect all parts of the world at an increasing rate. There have been over 92 million confirmed cases of COVID-19 by mid-January 2021. The similarity of homological sequences between SARS-CoV-2 and other SARSCoVs is high. In addition, clinical symptoms of SARS-CoV-2 and other SARS viruses show similarities. However, some COVID-19 cases show neurologic signs like headache, loss of smell, hiccups and encephalopathy. The drugs used in the palliative treatment of the disease also have some neurotoxic effects. Currently, there are approved vaccines for COVID-19. However, there is a need for specific therapeutics against COVID-19. This review will describe the neurological effects of SARS-CoV-2 and the neurotoxicity of COVID-19 drugs used in clinics. Drugs used in the treatment of COVID-19 will be evaluated by their mechanism of action and their toxicological effects.

Abstract: Severe Acute Respiratory Syndrome (SARS) aka SARS-CoV spread over southern China for the first time in 2002-2003 and history repeated again since last year and took away lives of more than two million people so far. On March 11, 2020 COVID-19 outbreak was officially declared as pandemic by World Health Organization (WHO). The entire world united to fight back against this ultimate destruction. Around 90 vaccines are featured against SARS-CoV-2 and more than 300 active clinical trials are underway by several groups and individuals. So far, no drugs have been currently approved that can completely eliminate the deadly coronavirus. The promising SARS-CoV-2 antiviral drugs are favipiravir, remdesivir, lopinavir, ribavirin and avifavir. In this review, we have discussed the synthetic approaches elaborately made so far by different groups and chemical companies all around the world towards top three convincing anti-viral drugs against SARS-CoV-2, which are favipiravir, remdesivir and lopinavir.

Abstract: The incidence of cancer is increasing worldwide, affecting a vast majority of the human population, therefore, new different anticancer agents are being developed now and their safety still needs to be evaluated. Among them, pyridine based drugs are contributing a lot, as they are one of the imperative pharmacophores occurring synthetically as well as naturally in heterocyclic compounds, having a wide-range of therapeutic applications in the area of drug discovery that offers many chances for further improvement in antitumor agents via acting onto numerous receptors of extreme prominence. Many pyridine derivatives are reported to inhibit enzymes, receptors and many other targets for controlling and curing the global health issue of cancer. Nowadays in combination with other moieties, researchers are focusing on the development of pyridine-based new derivatives for cancer treatment. Therefore, this review sheds light on the recent therapeutic expansion of pyridine together with its molecular docking, structure-activity-relationship, availability in the market, a summary of recently patented and published research works that shall jointly help the scientists to produce effective drugs with the desired pharmacological activity.

Abstract: Due to the high mortality rate of the 2019 coronavirus disease (COVID-19) pandemic, there is an immediate need to discover drugs that can help before a vaccine becomes available. Given that the process of producing new drugs is so long, the strategy of repurposing existing drugs is one of the promising options for the urgent treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease. Although FDA has approved Remdesivir for the use in hospitalized adults and pediatric patients suffering from COVID-19, no fully effective and reliable drug has been yet identified worldwide to treat COVID-19 specifically. Thus, scientists are still trying to find antivirals specific to COVID-19. This work reviews the chemical structure, metabolic pathway, and mechanism of action of the existing drugs with potential therapeutic applications for COVID-19. Furthermore, we summarized the molecular docking stimulation of the medications related to key protein targets. These already established drugs could be further developed, and after their testing through clinical trials, they could be used as suitable therapeutic options for patients suffering from COVID-19.

Abstract: Astaxanthin (AST) is a naturally occurring compound isolated from various sources such as fungi, plants, salmon, and crab. However, Haematococcus Pluvialis, a green alga, is the primary source of this beta carotenoid compound. AST has several favourable biological and pharmacological activities such as antioxidant, anti-inflammatory, anti-tumor, anti-diabetes, hepatoprotective, and neuroprotective activities. Nevertheless, the exact molecular mechanisms of these protective effects of AST are unclear yet. The Nrf2 signaling pathway is one of the critical candidate signaling pathways that may be involved in these beneficial effects of AST. This signaling pathway is responsible for maintaining the redox balance in the physiological state. Upon nuclear translocation, Nrf2 signaling activates antioxidant enzymes to reduce oxidative stress and protect cells against damage. In the current study, we have reviewed the effects of AST on the Nrf2 signaling pathway, which could potentially be developed as a novel therapeutic approach for the management of various diseases.

Background: Flavonoid glucuronides are a kind of natural products presenting a flavone linked directly with one or several glucuronides through O-glycoside bond. They had become of interest in natural product research in the past decades for their antioxidant, anti-inflammatory, and antibacteria activities. In particular, the compound breviscapine has a notable effect on cardiocerebrovascular diseases. Several other compounds even have antitumor activity. Methods: Through searching the database and reading a large number of documents, we summarized the related findings of flavonoid glucuronides. Results: We summarized 211 naturally occurring flavonoid glucuronides in 119 references with their chemical structures, biological activities, and metabolism. A total of 220 references from 1953 to 2020 were cited in this paper according to literature databases such as CNKI, Weipu, Wanfang data, Elsevier, Springer, Wiley, NCBI, PubMed, EmBase, etc. Conclusion: Flavonoid glucuronides are a class of compounds with various chemical structures and a diverse range of biological activities. They are thought to be potential candidates for drug discovery, but the specific study on their mechanisms is still limited until now. We hope this article can provide references for natural product researchers and draw more attention to flavonoid glucuronides’ biological activities and mechanisms.

Abstract: Learning and memory are two of our mind's most magical abilities. Different brain regions have roles to process and store different types of memories. The hippocampus is the part of the brain responsible for receiving information and storing it in the neocortex. One of the most impressive characteristics of the hippocampus is its capacity for neurogenesis which is a process, new neurons are produced and then transformed into mature neurons and integrated into neural circuits. The neurogenesis process in the hippocampus, an example of neuroplasticity in the adult brain, is believed to aid hippocampal-dependent learning and memory. New neurons are constantly produced in the hippocampus and integrated into the pre-existing neuronal network, this allows old memories already stored in the neocortex to be removed from the hippocampus and replaced with new ones. Factors affecting neurogenesis in the hippocampus may also affect hippocampal-dependent learning and memory. The flavonoids can exert particularly powerful actions in mammalian cognition and improve hippocampaldependent learning and memory by positively affecting hippocampal neurogenesis.

Abstract: Benzimidazole is a nitrogen-containing fused heterocycle which has been extensively explored in medicinal chemistry. Benzimidizole nucleus has been found to possess various biological activities such as anticancer, antimicrobial, anti-inflammatory, antiviral, antitubercular and antidiabetic. A number of benzimidazoles such as bendamustine, pantoprazole have been approved for the treatment of various illnesses, whereas galeterone and GSK461364 are in clinical trials. The present review article gives an overview of the different biological activities exhibited by the benzimidazole derivatives as well as different methods used for the synthesis of benzimidazole derivatives in the past ten years.

Abstract: The treatment and management of tuberculosis (TB) is a major global concern. Approved drugs for the treatment of TB, to date, have displayed various modes of action which can be grouped into radical releasing and non-radical releasing anti-TB agents. Radical releasing agents are of special interest because they diffuse directly into the mycobacterium cell wall, interact with the host cell DNA, causing DNA strand breakages and fatal destabilization of the DNA helix inhibiting nucleic acid synthase. As a therapeutic agent with the aforementioned activity, nitroimidazoles and most especially bicyclic nitroimidazoles are currently in clinical use for the treatment of tuberculosis. However, the approved drugs, pretomanid (PR) and delamanid (DE) are limited in their nitric oxide radical (NO^•) releasing abilities to cause effective bactericidity. It is believed that their bactericidal activity can be improved by harnessing alternative strategies to increase NO^• release. The last decade has witnessed the strategic inclusion of NO-donors into native drugs to improve their activities and/or reverse resistance. The rationale behind this strategy is the targeting of NO^• release at specific therapeutic sites. This review, therefore, aims to highlight various radical releasing agents that may be effective in the treatment of TB. The review also investigates various structural modifications to PR and DE and suggests alternative strategies to improve NO^•release as well as some applications where NO-donor hybrid drugs have been used with good therapeutic effect.