New Trends On Biological Activities And Clinical Studies Of Quinolinic Analogues: A Review

2021 ◽  
Vol 22 ◽  
Author(s):  
Sandra Elizabeth Barbosa da Silva ◽  
José Arion da Silva Moura ◽  
Tiago Rafael de Sousa Nunes ◽  
Ivan da Rocha Pitta ◽  
Marina Galdino da Rocha Pitta
Keyword(s):  
Side Effects ◽  
Clinical Studies ◽  
Biological Activities ◽  
Mechanisms Of Action ◽  
Antimalarial Drugs ◽  
New Drugs ◽  
Phase Iii ◽  
Synthetic Compounds ◽  
Preclinical And Clinical Studies ◽  
Natural And Synthetic

: The quinolinic ring, present in several molecules, has a great diversity of biological activities. Therefore, this ring is in the structure composition of several candidates of drugs in preclinical and clinical studies, thus, it is necessary the grouping of these results to facilitate the design of new drugs. For this reason, some of the activities were selected for this review, such as: antimalarial, antimicrobial, anticancer, anti-inflammatory, antidiabetic, anti-rheumatic and antiviral. All publications of scientific articles chosen are dated between 2000 and 2020. In addition to presenting the structures of some natural and synthetic compounds with their activities, we list the clinical studies of phases III and IV of antimalarial drugs containing the quinoline nucleus and phase III clinical studies of hydroxychloroquine and chloroquine to assess their possible role in COVID-19. Finally, we show some of the mechanisms of action, as well as the side effects of some of the quinolinic derivatives.

scholarly journals Toxic Animal-Based Medicinal Materials Can Be Effective in Treating Endometriosis: A Scoping Review

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 145
Author(s):  
Su-In Hwang ◽  
Young-Jin Yoon ◽  
Soo-Hyun Sung ◽  
Ki-Tae Ha ◽  
Jang-Kyung Park
Keyword(s):  
Side Effects ◽  
Clinical Studies ◽  
Malignant Tumors ◽  
Experimental Studies ◽  
Herbal Medicines ◽  
Treatment Method ◽  
Reproductive Age ◽  
Dependent Growth ◽  
Gynecological Disorder ◽  
Preclinical And Clinical Studies

Animal toxins and venoms have recently been developed as cancer treatments possessing tumor cell growth-inhibitory, antiangiogenesis, and proapoptotic effects. Endometriosis is a common benign gynecological disorder in reproductive-age women, and no definite treatment for this disorder is without severe side effects. As endometriosis and malignant tumors share similar characteristics (progressive, invasive, estrogen-dependent growth, and recurrence), animal toxins and venoms are thought to be effective against endometriosis. The objective of this study was to outline studies using toxic animal-based medicinal materials (TMM) as endometriosis treatment and to explore its clinical applicability. Preclinical and clinical studies using TMM were searched for in four databases from inception to October 2020. A total of 20 studies of TMM on endometriosis were included. In eight clinical studies, herbal medicines containing TMM were effective in relieving symptoms of endometriosis, with no side effects. In twelve experimental studies, the main therapeutic mechanisms of TMM against endometriosis were proapoptotic, antiangiogenesis, estrogen level-reducing, and possible anti-inflammatory effects. TMM are thus considered promising sources for the development of an effective treatment method for endometriosis. Further studies are needed to clarify the therapeutic mechanism of TMM against endometriosis and to provide sufficient grounds for clinical application.

scholarly journals A Preclinical Evaluation of the Antitumor Activities of Edible and Medicinal Mushrooms: A Molecular Insight

2017 ◽  
Vol 17 (2) ◽  
pp. 200-209 ◽  
Author(s):  
Thomson Patrick Joseph ◽  
Warren Chanda ◽  
Arshad Ahmed Padhiar ◽  
Samana Batool ◽  
Shao LiQun ◽  
...  
Keyword(s):  
Side Effects ◽  
Biological Activities ◽  
Genetic Alterations ◽  
In Vivo Models ◽  
Medicinal Mushrooms ◽  
Chemotherapy Drugs ◽  
Development Of Resistance ◽  
Preclinical And Clinical Studies

Cancer is the leading cause of morbidity and mortality around the globe. For certain types of cancer, chemotherapy drugs have been extensively used for treatment. However, severe side effects and the development of resistance are the drawbacks of these agents. Therefore, development of new agents with no or minimal side effects is of utmost importance. In this regard, natural compounds are well recognized as drugs in several human ailments, including cancer. One class of fungi, “mushrooms,” contains numerous compounds that exhibit interesting biological activities, including antitumor activity. Many researchers, including our own group, are focusing on the anticancer potential of different mushrooms and the underlying molecular mechanism behind their action. The aim of this review is to discuss PI3K/AKT, Wnt-CTNNB1, and NF-κB signaling pathways, the occurrence of genetic alterations in them, the association of these aberrations with different human cancers and how different nodes of these pathways are targeted by various substances of mushroom origin. We have given evidence to propose the therapeutic attributes and possible mode of molecular actions of various mushroom-originated compounds. However, anticancer effects were typically demonstrated in in vitro and in vivo models and very limited number of studies have been conducted in the human population. It is our belief that this review will help the research community in designing concrete preclinical and clinical studies to test the anticancer potential of mushroom-originated compounds on different cancers harboring particular genetic alteration(s).

scholarly journals Natural Polyphenols Targeting Senescence: A Novel Prevention and Therapy Strategy for Cancer

2020 ◽  
Vol 21 (2) ◽  
pp. 684 ◽  
Author(s):  
Yan Bian ◽  
Juntong Wei ◽  
Changsheng Zhao ◽  
Guorong Li
Keyword(s):  
Side Effects ◽  
Tumor Microenvironment ◽  
Cancer Prevention ◽  
Human Health ◽  
Clinical Studies ◽  
Natural Polyphenols ◽  
Therapy Strategy ◽  
Anti Cancer ◽  
Preclinical And Clinical Studies ◽  
Prevention And Therapy

Cancer is one of the most serious diseases endangering human health. In view of the side effects caused by chemotherapy and radiotherapy, it is necessary to develop low-toxic anti-cancer compounds. Polyphenols are natural compounds with anti-cancer properties and their application is a considerable choice. Pro-senescence therapy is a recently proposed anti-cancer strategy and has been shown to effectively inhibit cancer. It is of great significance to clarify the mechanisms of polyphenols on tumor suppression by inducing senescence. In this review, we delineated the characteristics of senescent cells, and summarized the mechanisms of polyphenols targeting tumor microenvironment and inducing cancer cell senescence for cancer prevention and therapy. Although many studies have shown that polyphenols effectively inhibit cancer by targeting senescence, it warrants further investigation in preclinical and clinical studies.

scholarly journals Monotherapy or Polytherapy for Epilepsy?

1998 ◽  
Vol 25 (S4) ◽  
pp. S3-S8 ◽  
Author(s):  
Alan Guberman
Keyword(s):  
Side Effects ◽  
Seizure Control ◽  
Lower Cost ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
First Line ◽  
New Antiepileptic Drugs ◽  
Epilepsy Treatment ◽  
Multiple Drugs ◽  
The Ideal

ABSTRACT:Monotherapy has been promoted as the ideal in epilepsy treatment because of reduced side effects, absence of drug interactions, better compliance, lower cost and, in many cases, improved seizure control compared to polytherapy. The question of monotherapy vs. polytherapy has assumed increasing importance with the availability of multiple new antiepileptic drugs (AEDs), initially tested as add-on agents. The new drugs clobazam, lamotrigine, vigabatrin, gabapentin and topiramate, have also been shown to be effective as monotherapy. These data bring up the possibility of using them as first-line agents. However, a high percentage of patients with resistant epilepsy are treated with polytherapy, which probably benefits only a minority of them. The availability of multiple drugs with different mechanisms of action favours the possibility of "rational polytherapy", taking advantage of possible synergism, a yet unproven concept. This article reviews the theoretical advantages of monotherapy and monotherapy with traditional and newer AEDs.

scholarly journals Review of properties and mechanisms of action of hepatoprotective drugs

2020 ◽  
pp. 36-44
Author(s):  
Е.В. Кардаш ◽  
Е.М. Григорьева ◽  
А.Г. Емельянова ◽  
С.А. Тарасов
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Side Effects ◽  
Randomized Clinical Trials ◽  
Evidence Base ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Simultaneous Administration ◽  
Essential Phospholipids ◽  
Meta Analyses

В медицинской практике достаточно часто возникает необходимость в одновременном приеме нескольких лекарственных средств. Иногда это оказывается невозможным в силу наличия у препаратов гепатотоксических свойств, поэтому актуальными задачами фармакологии являются как поиск и разработка новых препаратов, так и оптимизация уже существующих с целью уменьшения побочных эффектов при их приеме. В настоящем обзоре были проанализированы данные о фармакологических препаратах класса гепатопротекторов, разобраны механизмы их действия и потенциал поиска новых препаратов. В заключение отмечено, что в настоящее время в клинической практике наибольшей популярностью пользуются препараты, содержащие эссенциальные фосфолипиды и препараты, улучшающие рециркуляцию и выведение желчных кислот. Существуют теоретические обоснования механизмов действия этих препаратов и перспектива накопления доказательной базы для них в виде рандомизированных клинических исследований и мета-анализов. Medical practice quite often requires simultaneous administration of several drugs. Sometimes it is impossible due to their hepatotoxicity; therefore, urgent tasks of pharmacology include searching for and developing new drugs as well as optimizing already existing products in order to reduce side effects during their administration. This review focused on pharmacological drugs of the hepatoprotector class and their mechanisms of action and evaluated the prospects of searching for new medicines. In conclusion, drugs containing essential phospholipids and those improving recirculation and removal of bile acids are currently the most popular agents in clinical practice. Mechanisms of action of these drugs are theoretically justified and there is a prospect for building an evidence base for them by randomized clinical trials and meta-analyses.

scholarly journals THE CONCEPT AND MANAGEMENT OF WAJAUL MAFASIL IN UNANI MEDICINE

2021 ◽  
pp. 7-13
Author(s):  
ZEHRA ZAIDI
Keyword(s):  
Side Effects ◽  
Clinical Studies ◽  
Pharmacological Therapy ◽  
Phase Iii ◽  
Herbal Drugs ◽  
Effective Management ◽  
Unani Medicine ◽  
Herbal Medications ◽  
Classical Knowledge

More than 54 million Americans suffer from some form of arthritis and 23.7 million are limited in their usual activity, primarily due to pain. The study aims to highlight the concept of Arthralgia and the potential of its management in Unani Medicines. Osteoarthritis (OA) is a slowly progressive condition with a variable prognosis. In general, predicting the prognosis in patients with OA is difficult. However, pharmacological therapy can be associated with serious side effects and high costs. Therefore, alternative therapies have been under investigation. Herbal medications have shown the potential for safe and effective management of arthritis. The Unani Medicine is a rich source of classical knowledge on arthritis. OA has been mentioned as Wajaul Mafasil Balghami/Saudawi, and Unani Physicians has been treating this disease successfully with mostly single herbal drugs and their compound formulations for centuries. It has been revealed through animal, in vitro, and clinical studies that most of the single and compound Unani formulations are safe, without any side effects, and effective in OA, especially gout and rheumatoid arthritis. There is a need to conduct studies at Phase III level after analyzing 2nd Phase clinical studies of Unani medicine, so a promising safe, economic, and effective treatment can be provided to the ailing society for OA.

scholarly journals Plasmodium falciparum Resistance to a Lead Benzoxaborole Due to Blocked Compound Activation and Altered Ubiquitination or Sumoylation

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kirthana M. V. Sindhe ◽  
Wesley Wu ◽  
Jenny Legac ◽  
Yong-Kang Zhang ◽  
Eric E. Easom ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Stress Responses ◽  
Mechanisms Of Action ◽  
Antimalarial Drugs ◽  
New Drugs ◽  
Loss Of Function ◽  
Content Type ◽  
High Level ◽  
Level Resistance

ABSTRACT New antimalarial drugs are needed. The benzoxaborole AN13762 showed excellent activity against cultured Plasmodium falciparum, against fresh Ugandan P. falciparum isolates, and in murine malaria models. To gain mechanistic insights, we selected in vitro for P. falciparum isolates resistant to AN13762. In all of 11 independent selections with 100 to 200 nM AN13762, the 50% inhibitory concentration (IC50) increased from 18–118 nM to 180–890 nM, and whole-genome sequencing of resistant parasites demonstrated mutations in prodrug activation and resistance esterase (PfPARE). The introduction of PfPARE mutations led to a similar level of resistance, and recombinant PfPARE hydrolyzed AN13762 to the benzoxaborole AN10248, which has activity similar to that of AN13762 but for which selection of resistance was not readily achieved. Parasites further selected with micromolar concentrations of AN13762 developed higher-level resistance (IC50, 1.9 to 5.0 μM), and sequencing revealed additional mutations in any of 5 genes, 4 of which were associated with ubiquitination/sumoylation enzyme cascades; the introduction of one of these mutations, in SUMO-activating enzyme subunit 2, led to a similar level of resistance. The other gene mutated in highly resistant parasites encodes the P. falciparum cleavage and specificity factor homolog PfCPSF3, previously identified as the antimalarial target of another benzoxaborole. Parasites selected for resistance to AN13762 were cross-resistant with a close analog, AN13956, but not with standard antimalarials, AN10248, or other benzoxaboroles known to have different P. falciparum targets. Thus, AN13762 appears to have a novel mechanism of antimalarial action and multiple mechanisms of resistance, including loss of function of PfPARE preventing activation to AN10248, followed by alterations in ubiquitination/sumoylation pathways or PfCPSF3. IMPORTANCE Benzoxaboroles are under study as potential new drugs to treat malaria. One benzoxaborole, AN13762, has potent activity and promising features, but its mechanisms of action and resistance are unknown. To gain insights into these mechanisms, we cultured malaria parasites with nonlethal concentrations of AN13762 and generated parasites with varied levels of resistance. Parasites with low-level resistance had mutations in PfPARE, which processes AN13762 into an active metabolite; PfPARE mutations prevented this processing. Parasites with high-level resistance had mutations in any of a number of enzymes, mostly those involved in stress responses. Parasites selected for AN13762 resistance were not resistant to other antimalarials, suggesting novel mechanisms of action and resistance for AN13762, a valuable feature for a new class of antimalarial drugs.

Fastidious Anatomization of Biota Procured Compounds on Cancer Drug Discovery

2020 ◽  
Vol 21 (5) ◽  
pp. 354-363
Author(s):  
Anand Thirupathi ◽  
Chandra M. Shanmugavadivelu ◽  
Sampathkumar Natarajan
Keyword(s):  
Natural Products ◽  
Side Effects ◽  
Cancer Therapy ◽  
Biological Activities ◽  
Drug Approval ◽  
Current Treatment ◽  
New Drugs ◽  
Cancer Drug ◽  
Synthetic Drugs ◽  
Wide Range

Background: Natural products are the rootstock for identifying new drugs since ancient times. In comparison with synthetic drugs, they have abounding beneficial effects in bestowing protection against many diseases, including cancer. Cancer has been observed as a major threat in recent decades, and its prevalence is expected to increase over the next decades. Also, current treatment methods in cancer therapy such as radiation therapy and chemotherapy cause severe adverse side effects among the cancer population. Therefore, it is exigent to find a remedy without any side effects. Methods: In recent years, research has focused on obtaining naturally derived products to encounter this complication. The current pace of investigations, such as gene identification and advancement in combinatorial chemistry, leads to the aberrant access to a wide range of new synthetic drugs. In fact, natural products act as templates in structure predictions and synthesis of new compounds with enhanced biological activities. Results: Recent developments in genomics have established the importance of polymorphism, which implies that patients require different drugs for their treatment. This demands the discovery of a large number of drugs, but limited sources restrict the pharmaceutical industry to overcome these major obstacles. The use of natural products and their semisynthetic and synthetic analogues could alleviate these problems. However, the lack of standardization in terms of developing methods for evaluating the chemical composition, efficacy, isolation and international approval is still a major limitation in this field. In the past few years, several drug-approval authorities, including the FDA and WHO have allowed using these naturally derived compounds in humans. Conclusion: In this review, we described the use of some natural products from plant and marine sources in cancer treatment and shed some light on semi-synthetic and synthetic compounds derived from natural sources used in cancer therapy.

Reposition of the Fungicide Ciclopirox for Cancer Treatment

2021 ◽  
Vol 16 ◽  
Author(s):  
Zhu Huang ◽  
Shile Huang
Keyword(s):  
Cancer Treatment ◽  
Anticancer Activity ◽  
Anticancer Agents ◽  
Clinical Studies ◽  
Water Solubility ◽  
Iron Chelation ◽  
Mechanisms Of Action ◽  
Migration And Invasion ◽  
Preclinical And Clinical Studies ◽  
Multiple Signaling

Background: : Ciclopirox (CPX), a broad-spectrum fungicide, has been widely used to treat fungal infection on the skin and nails for decades. Recent preclinical and clinical studies have shown that CPX also possesses promising anticancer activity. Objective: To summarize the patents, the pharmacological and toxicological properties, the anticancer activity, and the mechanisms of action of CPX and its derivatives as anticancer agents. Methods: We searched PubMed and Google using the keywords “ciclopirox”, “cancer or tumor” and “patent”, and reviewed the literature identified. Results: Pharmacological and toxicological profiles from preclinical and clinical studies support that systemic administration of CPX and its derivatives is feasible and safe for cancer treatment. CPX exerts its anticancer activity by inhibiting cell proliferation, inducing apoptosis, suppressing cell migration and invasion, and inhibiting angiogenesis and lymphangiogenesis. Mechanistically, CPX impacts the expression or activities of multiple signaling molecules or pathways, such as ribonucleotide reductase, Myc, DJ-1, Wnt/β-catenin, DOHH/eIF5A/PEAK1, VEGFR-3/ERK1/2, ATR/Chk1/Cdc25A, and AMPK/TSC/mTORC1. Most of these effects are attributed to iron chelation by CPX. Five patents have been retrieved: four patents on the development of CPX prodrugs to improve the water solubility and bioavailability of CPX, and one patent on the methods of bladder cancer treatment with CPX, CPX-O, or a CPX prodrug. Conclusion: CPX has a great potential to be repositioned for cancer therapy.

scholarly journals Plants of the Genus Lavandula: From Farm to Pharmacy

2018 ◽  
Vol 13 (10) ◽  
pp. 1934578X1801301 ◽  
Author(s):  
Bahare Salehi ◽  
Dima Mnayer ◽  
Beraat Özçelik ◽  
Gokce Altin ◽  
Kadriye Nur Kasapoğlu ◽  
...  
Keyword(s):  
North Africa ◽  
Clinical Studies ◽  
Viral Infections ◽  
Biological Activities ◽  
Perillyl Alcohol ◽  
Mechanisms Of Action ◽  
Health Conditions ◽  
Linalyl Acetate ◽  
High Concentrations

The Lavandula genus, belonging to the Lamiaceae, includes 39 species, with nearly 400 registered cultivars. Lavandula are worldwide plants that occur over the Mediterranean, Europe, North Africa, southwest Asia to southeast India. Lavandula plants have been used since ancient time to flavor and preserved food, to treat diseases including wound healing, sedative, antispasmodic, microbial and viral infections. Numerous researches have described the chemical composition and the primary components of lavender oils are the monoterpenoids (linalool, linalyl acetate, 1,8-cineole, β-ocimene, terpinen-4-ol, and camphor), sesquiterpenoids (β-caryophyllene and nerolidol) and other terpenoid compounds (e.g., perillyl alcohol). The high concentrations of linalyl acetate make them attractive in perfumery, flavoring, cosmetics and soap industries. Currently, data on the antimicrobial activity of lavender plants have been scientifically confirmed. Indeed, lavender essential oils possess wide spectra of biological activities such as antispasmodic, carminative, analgesic, sedative, hypotensive, antiseptic, antimicrobial, antifungal, antidiuretic and general tonic action. In addition, clinical studies support their uses as treatment of health conditions. However, further clinical studies are necessary to define the magnitude of the efficacy, mechanisms of action, optimal doses, long-term safety, and, potential side effects of lavender plants.

Sign in / Sign up

Export Citation Format

Share Document