Mini Reviews in Medicinal Chemistry - Volume 21, Issue 20, 2021

Background: Major approach in controlling as well as eradicating the cancerous growth is through radiotherapy, but this treatment leads to toxicity in the normal cells, leading to secondary malignancies, teratogenesis, and necrosis. More than 15,000 malignancies occur due to exposure to harmful radiations during computed tomography scans. Natural products are non-toxic; there have been reports that herbal products, when given along with radiation, have shown increased tumor control property. The discussed agents in this review have potential antioxidant, immunomodulatory, free radical scavenging, metal chelating, and anti-inflammatory properties. Objective: To reduce the chances of toxicity, reduction in radiation dose or reducing the frequency of the therapy is made which usually leads to a therapeutically poor outcome. The most feasible method is to protect the normal cells by administration of radioprotective agents either before or after the exposure. These agents have been tested on animals and human cell models for evaluating their safety window and toxicity profile at the cellular level. The study aims to compile the effective natural radioprotective agents available, which can be further exploited by using certain QSAR studies to increase their potency. Method: Structured literature search from EMBASE, PubMed, Bentham Science, Scopus, and ScienceDirect was carried out and appropriate peer-reviewed review articles, as well as certain research articles, were included and compiled in this review paper. Conclusion: As various studies have indicated the harmful effects of ionizing radiations on normal cells, to reduce these effects, radioprotective agents are used before or after exposure to radiations. Compounds derived from natural sources are proved to have few side effects and they possess radioprotective property due to the presence of alkaloids, resins, volatile oils, tannins in their molecular structure. Various plants having such radioprotective constitutes have been identified for their radioprotective action and compiled in the present study.

Abstract: Carica papaya is an essential medicinal plant having anticancer activities through diverse mechanisms and is not so far thoroughly investigated. In this review, we have summarized the systematic research outputs of different parts of the papaya plant extracts and elaborated the role of its phytochemicals, anticancer activities, therapeutic targets and mechanisms. Several phenolic compounds have been identified from this plant. Of these, Caffeic acid, Quinic acid and Chlorogenic acid show significant properties and act as principal bioactive phytoconstituents among others. We have explored the nutraceutical and functional aspects of Caffeic acid, Quinic acid and Chlorogenic acid along with the new understanding of the mechanism and its action in diverse cancer models. Also, we have highlighted its bioavailability, natural food additive properties and cost-effectiveness.

Abstract: Garcinia pedunculata Roxb.(GP) belongs to the family of Clusiaceae and is an evergreen tree that grows in semi-wild conditions and is widely distributed throughout the Northeastern part of India. Traditionally, this plant is believed to be of immense medicinal importance and is used for the treatment of various ailments. In Assam, the acidic fruit of GP is effectively used in folklore medicine to treat gastrointestinal disorders and is an integral part of ethnic Assamese cuisine. The ripe fruit, seldom consumed fresh or raw, is cut into thin slices, sun-dried for preservation as it is believed that the medicinal property of the fruit increases as it ages. With much traditional claims and beliefs regarding the medicinal properties of this plant, many therapeutic potentials of GP have been explored through research till now, including its antioxidant, antibacterial, antifungal, anthelmintic, hypolipidemic, antidiabetic, hepatoprotective, neuroprotective, and nephroprotective properties. Moreover, the presence of polyphenols, flavonoids along with bioactive components like hydroxycitric acid, garcinol, and cambogin have also been reported from this plant, thereby increasing its research avenues. Even with the available knowledge, there is a huge lacking in the understanding of its underlying molecular mechanism responsible for the therapeutic properties, pharmacological mode of action, and its effect in different pathological conditions, along with detailed information about its chemical composition. This review mainly aims to summarise the potentially beneficial properties of GP that have already been reported, along with identifying the new avenues that still need to be addressed, thereby increasing the future prospect for in-depth research on this plant, along with its distribution and conservation status.

Abstract: Breast cancer is the most frequently diagnosed cancer in women and the second most common form of cancer, causing death after lung cancer, all across the globe at an alarming rate. The level of estrogens in breast cancer tissues of postmenopausal women is 10-40 folds higher than the non-carcinogenic breast tissues. As a result of this greater level of estrogen, breast tissue becomes more prone to develop breast cancer; mainly, estradiol plays a significant role in the initiation and development of hormone-dependent breast cancer. Androstenedione, Adrenal dehydroepiandrosterone sulfate, and estrone-sulfate also play an important role as precursors for estrogen biosynthesis. Estrogen deprivation exhibits an attractive phenomenon in the advancement of ideal therapeutics for the treatment of breast cancer. Inhibition of aromatase and sulphatase emerged as an attractive therapy for the treatment of hormone-dependent breast cancer via deprivation of estrogen by different pathways. The cocktail of aromatase and sulphatase inhibitors known as Dual Aromatase-sulphatase Inhibitors (DASIs) emerged as an attractive approach for effective estrogen deprivation. The present review article focused on the journey of dual aromatase-sulphatase inhibitors from the beginning to date (2020). Keeping in view the key observations, this review may be helpful for medicinal chemists to design and develop new and efficient dual aromatase-sulphatase inhibitors for the possible treatment of hormone- related breast cancer.

Abstract: The cardiovascular complications of Type 2 Diabetes Mellitus (T2DM) including myocardial infarction, heart failure, peripheral vascular disease and, stroke and retinopathy, nephropathy and neuropathy are microvascular complications. While the newer therapies like glitazones or even Dipeptidyl- peptidase-IV (DPP-IV) inhibitors increase the risk of therapy, the Glucagon Like Peptide-1 Receptor Agonists (GLP-1RAs), were reported as suitable alternates. The GLP-1RAs reduce Major Adverse Cardiovascular Events (MACE), have anti-atherogenic potential, and possess pleiotropic activity. The GLP-1RAs were found to improve neuroprotection, enhance neuronal growth, reduce the incidence of stroke, and improve central insulin resistance. The GLP-1RAs are beneficial in improving the glycemic profile, preventing macroalbuminuria and reducing the decline in eGFR and enhancing renal protection. The renal benefits of add-on therapy of GLP-1RAs with SGLT-2 inhibitors have composite renal outcomes such as suppression of inflammatory pathways, improvement in natriuresis, diuresis, found to be nephroprotective. Improvement in glycemic control with a reduction in body weight and intraglomerular pressure and prevention of tubular injury makes the GLP-1RAs as suitable add-on therapies in improving cardiorenal outcomes. Obesity, an important contributor to insulin resistance and a reduction in weight, is an essential therapeutic option in addressing diabetic-obesity. It also reduces the damage to blood-retinal-barrier, thus beneficial in halting the development of diabetic retinopathy. In diabetic complications, glycemic control, addressing insulin resistance through weight loss, controlling atherosclerosis through anti-inflammatory effects and cardio-renal-neuro protection, makes GLP-1RAs a suitable therapeutic strategy on long-term treatment of T2DM. This review discusses the role of GLP-1RAs in diabetes, the dosage, mono or combination therapy with other antidiabetics in long-term treatment and its effect in uncontrolled diabetes.

Abstract: Bilastine (BIL) is the new generation antihistamine that is used to relieve the symptoms of hayfever, chronic urticaria and other forms of allergic rhinitis. Chemically it is known 2-[4-[2-[4-[1- (2-ethoxyethyl) benzimidazole-2-yl] piperidine-1-yl] ethyl] phenyl]-2-methylpropane acid. The chemical structure of BIL having a hydrophilic carboxylic substituent. BIL has a longer duration of action due to its potent binding affinity to the H1 receptor. This review summarizes the properties, characteristics, chemistry along with analytical and bioanalytical methods used for estimation of BIL from different scientific articles. The literature has demonstrated some methods for quantification of BIL in various sample matrix and pharmaceutical products. Frequently and extensively used antihistaminics are in the clinic practice, a novel, effective, economic and safe analytical methodology is required for routine quality control analysis, bioavailability, and bioequivalence studies. Furthermore, this narrative review summarizes available data on chemistry, pharmacology and analysis of BIL in a different matrix.

Abstract: Corona Virus Disease-2019 (COVID-19), caused by the SARS CoV-2 virus, has been announced as a pandemic by the World Health Organization. COVID-19 has affected people globally, infecting more than 39.8 million people and claiming up to 1.11 million lives, yet there is no effective treatment strategy to cure this disease. As vaccine development is a time-consuming process, currently, efforts are being made to develop alternative plans for the timely and effective management of this disease. Drug repurposing always fascinated researchers and can be utilized as the most acceptable alternative to develop the therapeutics for COVID-19 using the pre-approved drugs. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has shown resemblance with distinctive enzyme targets, such as 3CLpro/Mpro, RdRp, Cathepsin L, and TMPRSS2 present in SARS CoV and MERS CoV. Therefore, the drugs that have shown efficacy in these viruses can also be used for the treatment of COVID-19. This review focuses on why repurposing could provide a better alternative in COVID- 19 treatment. The similarity in the structure and progression of infection of SARS CoV and MERS viruses offers a direction and validation to evaluate the drugs approved for SARS and MERS against COVID-19. It has been indicated that multiple therapeutic options that demonstrate efficacy against SARS CoV 2 are available to mitigate the potential emergence of COVID-19 infection.

Abstract: The small-molecular inhibitors targeted JAks (JAK inhibitors) could modulate the cytokines- mediated signaling via the JAK-STAT pathway, which plays an important role in immune regulation and cell proliferation. The JAK inhibitors were previously designed and synthesized to treat diseases involving the hematologic and immune system. Increasing evidence shows that they are quite effective in Atopic Dermatitis (AD), Alopecia Areata (AA), psoriasis, vitiligo, and other autoimmuneinduced dermatologic conditions. Currently, many JAK inhibitors possessing anti-vitiligo activity are being investigated in the laboratory and clinically. In this view, we would like to summarize the applications of these inhibitors with emphasis on the profile of vitiligo, clinical efficacy, dosages, development of new candidates and adverse events through available literature.

Abstract: Dementia is a chronic neurodegenerative disease, and a maximum number of the cases are directly related to Alzheimer’s disease. More than 4 million people are living with Alzheimer’s disease-related dementia in India, making it a national crisis. Alzheimer’s disease deteriorates cognitive functions with the passage of time and consists of multi-faceted factors, such as the decline of acetylcholine level, amyloid β-aggregation, tau hyperphosphorylation, oxidative stress, etc. The classical drugs used to date, are focused on only one target and are not serving the cause properly. Hence, the community of scientists is rigorously working on multi-target-directed agents that incorporate two or more active scaffolds in one compound or hybrid of active moieties. This article aims to evaluate novel potential compounds and moieties, such as quinolines, chalcones, coumarins, chromenes, piperazine, carbazoles, cinnamic acids, tacrine hybrids, donepezil hybrids, etc., that have been introduced as multi-target-directed agents in the recent five years.