Chlorogenic Acid Derivatives: Structural Modifications, Drug Design, and Biological Activities: A Review.

BACKGROUND: Phenolic acids have recently gained considerable attention because of their numerous practical, biological, and pharmacological benefits. Various polyphenolic compounds are widely distributed in plant sources. Flavonoids and phenolic acids are the two main polyphenolic compounds that many plants contain abundant polyphenols. Chlorogenic acid, one of the most abundant phenolic acids, has various biological activities, but it is chemically unstable and degrades into other compounds or different enzymatic processes. METHODS: In this review, we have studied many publications about CA and its derivatives. CA derivatives were classified into three categories in terms of structure and determined each part's effects on the body. The biological evaluations, structure-activity relationship, and mechanism of action of CA derivatives were investigated. The search databases for this review were ScienceDirect, Scopus, PubMed and google scholar. RESULTS: Many studies have reported that CA derivatives have demonstrated several biological effects, including anti-oxidant, anti-inflammatory, anti-microbes, anti-mutation, anti-carcinogenic, anti-viral, anti-hypercholesterolemia, anti-hypertensive, anti-bacterial, and hypoglycemic actions. The synthesis of new stable CA derivatives can enhance its metabolic stability and biological activity. CONCLUSION: The present study represented different synthetic methods and biological activities of CA derivatives. These compounds showed high antioxidant activity across a wide range of biological effects. Our goal was to help other researchers design and develop stable analogs of CA for the improvement of its metabolic stability and the promotion of its biological activity.

Drug design strategies that aim to improve the low solubility and poor bioavailability conundrum in quercetin derivatives.

INTRODUCTION: Scientists are especially interested in polyphenols, particularly flavonoids. Quercetin, a flavonoid, has demonstrated various therapeutic properties, such as antioxidant, anti-diabetic, anti-hypertensive, and anti-carcinogenic activities. Different plant sources contain varying quantities and types of quercetin. However, quercetin's bioavailability is frequently low due to its low water solubility, molecular stability, and absorption characteristics. AREAS COVERED: The primary goals of this review are related to the approaches for overcoming quercetin's limitations. Hence, the main tactics for structural modifications (addition of charged and polar groups, removing C2, C3 double bond or reducing aromaticity, disrupting intramolecular H-bond, and reducing crystal lattice stability) and drug delivery systems (cyclodextrin complexes, emulsions, nanoparticles, liposomes, etc.) were discussed to improve water solubility and bioavailability of quercetin. EXPERT OPINION: From a tactical perspective, enhancing the solubility of compounds can be simplified through decreasing hydrophobic properties or crystalline stability. In addition, an essential field of study focuses on creating appropriate molecular carriers for substances with low water solubility. However, pharmacokinetics, potency, and toxicology are all impacted by the structural factors and physical characteristics that regulate solubility. Poor water solubility is still a major problem in drug discovery, and new methods are always in demand to overcome it.

O-Glycoside quercetin derivatives: Biological activities, mechanisms of action, and structure-activity relationship for drug design, a review.

Quercetin as a valuable natural flavonoid has shown extensive biological activities, including anticancer, antioxidant, antibacterial, antiinflammatory, anti-Alzheimer, antifungal, antiviral, antithalassemia, iron chelation, antiobesity, antidiabetic, antihypertension, and antiphospholipase A2 (PLA2) activities, by the modulation of various targets and signaling pathways that have attracted much attention. However, the low solubility and poor bioavailability of quercetin have limited its applications; therefore, the researchers have tried to design and synthesize many new derivatives of quercetin through different strategies to modify quercetin restrictions and improve its biological activities. This review categorized the O-glycoside derivatives of Quercetin into two main classes, 3-O-glycoside and other O-glycoside derivatives. Also, it studied biological activities, structure-activity relationship (SAR), and the action mechanism of O-glycoside quercetin derivatives. Overall, we summarized past and present research for discovering new potent lead compounds. HIGHLIGHTS: Quercetin is a natural flavonoid with a valuable scaffold. O-Glycoside quercetin derivatives represents broad-spectrum biological activities. The structure-activity relationship investigation is discussed after modifying the scaffold of quercetin. This review can help researchers to rationally design/develop various drugs.

Quercetin derivatives: Drug design, development, and biological activities, a review.

More studies are needed to develop new drugs for problems associated with drug resistance and unfavorable side effects. The natural flavonoid of quercetin revealed a wide range of biological activities by the modulation of various targets and signaling pathways. However, quercetin's low solubility and poor bioavailability have restricted its applicability; as a result, researchers have attempted to design and synthesize numerous novel quercetin derivatives using various methodologies in order to modify quercetin's constraints; the physico-chemical properties of quercetin's molecular scaffold make it appealing for drug development; low molecular mass and chemical groups are two of these characteristics. Therefore, the biological activities of quercetin derivatives, as well as the relationship between activity and chemical structure and their mechanism of action, were investigated. These quercetin-based molecules could be valuable in the creation and discovery of medications for a number of diseases.

Pyrazolotriazines: Biological activities, synthetic strategies and recent developments.

Heterocyclic compounds create an important class of molecules that demonstrates various chemical spaces for the definition of effective medicines. Many N-heterocycles display numerous biological activities. Among condensed heterocycles, pyrazolotriazine derivatives have received the attention of researchers owing to the extensive spectrum of biological activities. The reactivity of identified compounds was similar to the free azoles and triazines. The pyrazolotriazine scaffold exhibited antiasthma, antiinflammatory, anticancer, antithrombogenic activity and showed activity for major depression and pathological anxiety. Pyrazolotriazine derivatives also exhibited antibacterial, anticancer, antimetabolites, antidiabetic, antiamoebic, anticonvulsant, antiproliferative activity, human carbonic anhydrase inhibition, cyclin-dependent kinase 2 inhibition, tyrosinase and urease inhibition, MAO-B inhibition, TTK inhibition, thymidine phosphorylase inhibition, tubulin polymerization inhibition, protoporphyrinogen oxidase inhibition, GABAA agonistic activity, hCRF1 receptor antagonistic activity, and CGRP receptor antagonistic activity. This paper structurally categorized various pyrazolotriazines to isomeric classes into six groups that containing pyrazolo [1,5-d] [1,2,4] triazine, pyrazolo [5,1-c] [1,2,4] triazine, pyrazolo [3,4-e] [1,2,4] triazine, pyrazolo [4,3-e] [1,2,4] triazines, pyrazolo [1,5-a] [1,3,5] triazine, and pyrazolo [3,4-d] [1,2,3] triazine and expressed biological activity, the synthetic procedures for each class of pyrazolotriazines, structure-activity relationship and their mechanism of action. Generally, this review summarily indicated the past and present studies about the discovery of new lead compounds with good biological activity.

Antiviral Activities of Pyridine Fused and Pyridine Containing Heterocycles, A Review (from 2000 to 2020).

Heterocyclic compounds play a critical role in medicinal chemistry, and many available drugs contain heterocyclic rings. A six-membered heterocyclic compound, pyridine, showed various applications, including being an important solvent, reagent, and precursor in agrochemicals and pharmaceuticals. Due to the increase in drug resistance, there is an apparent medical need to develop new antiviral agents. Various derivatives of pyridine scaffold display broad biological activities such as anti-microbial, antiviral, antioxidant, anti-diabetic, anti-cancer, anti-malarial, analgesic, and antiinflammatory activities. Furthermore, they display psychopharmacological, antagonistic, anti-amoebic agents, and anti-thrombic activities. Due to the high importance of pyridine derivatives, in the present review, we tried to collect and classify many pyridine derivatives based on their structures from 2000 to 2020. Pyridine derivatives were classified into two general categories, including pyridine containing heterocycles and pyridine fused rings. The structure-activity relationship (SAR) and the action mechanism of derivatives were also investigated. According to the recent studies, these derivatives exhibited good antiviral activity against different types of viruses such as the human immunodeficiency viruses (HIV), the hepatitis C virus (HCV), the hepatitis B virus (HBV), respiratory syncytial virus (RSV), and cytomegalovirus (CMV). These derivatives inhibited viral application with different action mechanism such as RT inhibition, polymerase inhibition, inhibition of RNase H activity, inhibition of maturation, inhibition of the viral thymidine kinase, AAK1 (Adaptor-Associated Kinase 1) inhibition, GAK (Cyclin G-associated kinase) inhibition, inhibition of post-integrational event, inhibition of HDAC6, CCR5 antagonistic activity, DNA and RNA replication inhibition, gene expression inhibition, cellular NF-jB signaling pathway and neuraminidase (NA) inhibition, protein synthesis inhibition, and generally inhibition of viral replication cycle. This paper summarized the past and present results about the discovery of novel lead compounds with good antiviral activity. Studies exhibited that almost all of the evaluations were performed by way of in vitro testing. It is necessary to investigate in vivo and clinical testing for better evaluations in the future. We believe that pyridine derivatives can be used as promising antiviral agents and more broad investigations in this field need to be performed.

Development and therapeutic potential of 2-aminothiazole derivatives in anticancer drug discovery.

Currently, the development of anticancer drug resistance is significantly restricted the clinical efficacy of the most commonly prescribed anticancer drug. Malignant disease is widely prevalent and considered to be the major challenges of this century, which concerns the medical community all over the world. Consequently, investigating small molecule antitumor agents, which could decrease drug resistance and reduce unpleasant side effect is more desirable. 2-aminothiazole scaffold has emerged as a promising scaffold in medicinal chemistry and drug discovery research. This nucleus is a fundamental part of some clinically applied anticancer drugs such as dasatinib and alpelisib. Literature survey documented that different 2-aminothiazole analogs exhibited their potent and selective nanomolar inhibitory activity against a wide range of human cancerous cell lines such as breast, leukemia, lung, colon, CNS, melanoma, ovarian, renal, and prostate. In this paper, we have reviewed the progresses and structural modification of 2-aminothiazole to pursuit potent anticancers and also highlighted in vitro activities and in silico studies. The information will useful for future innovation. Representatives of 2-aminothiazole-containing compounds classification.