Sanguiins—Promising Molecules with Broad Biological Potential

Compounds of natural origin, an infinite treasure of bioactive chemical entities, persist as an inexhaustible resource for discovering new medicines. In this review, we summarize the naturally occurring ellagitannins, sanguiins, which are bioactive constituents of various traditional medicinal plants, especially from the Rosaceae family. In-depth studies of sanguiin H-6 as an antimicrobial, antiviral, anticancer, anti-inflammatory, and osteoclastogenesis inhibitory agent have led to potent drug candidates. In addition, recently, virtual screening studies have suggested that sanguiin H-6 might increase resistance toward SARS-CoV-2 in the early stages of infection. Further experimental investigations on ADMET (absorption, distribution, metabolism, excretion, and toxicity) supplemented with molecular docking and molecular dynamics simulation are still needed to fully understand sanguiins’ mechanism of action. In sum, sanguiins appear to be promising compounds for additional studies, especially for their application in therapies for a multitude of common and debilitating ailments.

Download Full-text

Astragalin: A Bioactive Phytochemical with Potential Therapeutic Activities

Advances in Pharmacological Sciences ◽

10.1155/2018/9794625 ◽

2018 ◽

Vol 2018 ◽

pp. 1-15 ◽

Cited By ~ 15

Author(s):

Ammara Riaz ◽

Azhar Rasul ◽

Ghulam Hussain ◽

Muhammad Kashif Zahoor ◽

Farhat Jabeen ◽

...

Keyword(s):

Experimental Investigations ◽

Caspase 9 ◽

Antiapoptotic Proteins ◽

Drug Candidates ◽

Naturally Occurring ◽

Cox 2 ◽

Potent Drug ◽

Cuscuta Chinensis ◽

Therapeutic Activities ◽

Cell Adhesion Proteins

Natural products, an infinite treasure of bioactive chemical entities, persist as an inexhaustible resource for discovery of drugs. This review article intends to emphasize on one of the naturally occurring flavonoids, astragalin (kaempferol 3-glucoside), which is a bioactive constituent of various traditional medicinal plants such as Cuscuta chinensis. This multifaceted compound is well known for its diversified pharmacological applications such as anti-inflammatory, antioxidant, neuroprotective, cardioprotective, antiobesity, antiosteoporotic, anticancer, antiulcer, and antidiabetic properties. It carries out the aforementioned activities by the regulation and modulation of various molecular targets such as transcription factors (NF-κB, TNF-α, and TGF-β1), enzymes (iNOS, COX-2, PGE2, MMP-1, MMP-3, MIP-1α, COX-2, PGE-2, HK2, AChe, SOD, DRP-1, DDH, PLCγ1, and GPX), kinases (JNK, MAPK, Akt, ERK, SAPK, IκBα, PI3K, and PKCβ2), cell adhesion proteins (E-cadherin, vimentin PAR-2, and NCam), apoptotic and antiapoptotic proteins (Beclin-1, Bcl-2, Bax, Bcl-xL, cytochrome c, LC3A/B, caspase-3, caspase-9, procaspase-3, procaspase-8, and IgE), and inflammatory cytokines (SOCS-3, SOCS-5, IL-1β, IL-4, IL-6, IL-8, IL-13, MCP-1, CXCL-1, CXCL-2, and IFN-γ). Although researchers have reported multiple pharmacological applications of astragalin in various diseased conditions, further experimental investigations are still mandatory to fully understand its mechanism of action. It is contemplated that astragalin could be subjected to structural optimization to ameliorate its chemical accessibility, to optimize its absorption profiles, and to synthesize its more effective analogues which will ultimately lead towards potent drug candidates.

Download Full-text

Recent Synthetic Strategies for Monocyclic Azole Nucleus and Its Role in Drug Discovery and Development

Current Organic Synthesis ◽

10.2174/1570179414666171013154337 ◽

2018 ◽

Vol 15 (3) ◽

pp. 321-340 ◽

Cited By ~ 5

Author(s):

Neha ◽

Ashish Ranjan Dwivedi ◽

Rakesh Kumar ◽

Vinod Kumar

Keyword(s):

Heterocyclic Compounds ◽

Biological Activities ◽

Review Article ◽

Drug Discovery And Development ◽

Drug Candidates ◽

Drug Molecules ◽

Current Review ◽

Biological Potential ◽

Recent Developments ◽

Potent Drug

Background: In recent years, the development and diversification of heterocyclic compounds has become central to the discovery of bioactive compounds with novel or improved pharmacological properties. In particular, N-containing heterocycles are proved to be promising leads and drug candidates, and received huge attention of the medicinal chemists. Objective: Many drugs especially antibiotics are becoming obsolete due to the development of multidrug resistance. Moreover, toxicity and other side effects of some drugs necessitated the quest for safer and more potent drug candidates. The current review article described biological potential of various monocyclic azoles. Recent developments in the synthesis of azole derivatives have been also reviewed. Conclusion: The presence of N-heterocyclic rings can influence the pharmacokinetics, pharmacodynamics, pKa and bioavailability profile of the drug molecules. Compounds containing monocyclic azole rings showed various biological activities and number of molecules are in clinical practice. A number of important leads and potential drug candidates containing azole nucleus are in advance stages of drug developments. Thus, simple, atom economic and more efficient synthetic strategies are desired for the synthesis of new libraries of the compounds.

Download Full-text

3-Phenylcoumarins as a Privileged Scaffold in Medicinal Chemistry: The Landmarks of the Past Decade

Molecules ◽

10.3390/molecules26216755 ◽

2021 ◽

Vol 26 (21) ◽

pp. 6755

Author(s):

Maria J. Matos ◽

Eugenio Uriarte ◽

Lourdes Santana

Keyword(s):

Medicinal Chemistry ◽

Review Paper ◽

Relevant Literature ◽

Natural Origin ◽

Drug Candidates ◽

Heterocyclic Molecules ◽

The Past ◽

New Drug ◽

Privileged Scaffold

3-Phenylcoumarins are a family of heterocyclic molecules that are widely used in both organic and medicinal chemistry. In this overview, research on this scaffold, since 2010, is included and discussed, focusing on aspects related to its natural origin, synthetic procedures and pharmacological applications. This review paper is based on the most relevant literature related to the role of 3-phenylcoumarins in the design of new drug candidates. The references presented in this review have been collected from multiple electronic databases, including SciFinder, Pubmed and Mendeley.

Download Full-text

Screening of FDA Approved Drugs Against COVID-19 Main Protease: Coronavirus Disease

10.20944/preprints202004.0062.v1 ◽

2020 ◽

Cited By ~ 4

Author(s):

Vijayakumar Balakrishnan ◽

Karthik Lakshminarayanan

Keyword(s):

Vaccine Development ◽

New Drugs ◽

World Health ◽

Wuhan City ◽

Drug Candidates ◽

Human Contact ◽

Main Protease ◽

Potent Drug ◽

Approved Drugs ◽

Fda Approved Drugs

In the end of December 2019, a new strain of coronavirus was identified in the Wuhan city of Hubei province in China. Within a shorter period of time, an unprecedented outbreak of this strain was witnessed over the entire Wuhan city. This novel coronavirus strain was later officially renamed as COVID-19 (Coronavirus disease 2019) by the World Health Organization. The mode of transmission had been found to be human-to-human contact and hence resulted in a rapid surge across the globe where more than 1,100,000 people have been infected with COVID-19. In the current scenario, finding potent drug candidates for the treatment of COVID-19 has emerged as the most challenging task for clinicians and researchers worldwide. Identification of new drugs and vaccine development may take from a few months to years based on the clinical trial processes. To overcome the several limitations involved in identifying and bringing out potent drug candidates for treating COVID-19, in the present study attempts were made to screen the FDA approved drugs using High Throughput Virtual Screening (HTVS). The COVID-19 main protease (COVID-19 Mpro) was chosen as the drug target for which the FDA approved drugs were initially screened with HTVS. The drug candidates that exhibited favorable docking score, energy and emodel calculations were further taken for performing Induced Fit Docking (IFD) using Schrodinger’s GLIDE. From the flexible docking results, the following four FDA approved drugs Sincalide, Pentagastrin, Ritonavir and Phytonadione were identified. In particular, Sincalide and Pentagastrin can be considered potential key players for the treatment of COVID-19 disease.

Download Full-text

Computational Discovery of SARS-CoV-2 NSP 16 Drug Candidates Based on Pharmacophore Modeling and Molecular Dynamics Simulation

Journal of Computational Biophysics and Chemistry ◽

10.1142/s2737416521500198 ◽

2021 ◽

Vol 20 (04) ◽

pp. 377-390

Author(s):

Zahra Hesari ◽

Samaneh Zolghadri ◽

Sajad Moradi ◽

Mohsen Shahlaei ◽

Elham Tazikeh-Lemeski

Keyword(s):

Molecular Dynamics ◽

Study Drug ◽

Pharmacophore Modeling ◽

Binding Energies ◽

Dynamics Simulation ◽

Structural Protein ◽

Drug Candidates ◽

Computational Discovery ◽

Approved Drugs ◽

Dynamics Simulations

Non-Structural Protein 16 (NSP-16) is one of the most suitable targets for discovery of drugs for corona viruses including SARS-CoV-2. In this study, drug discovery of SARS-CoV-2 nsp-16 has been accomplished by pharmacophore-based virtual screening among some analogs (FDA approved drugs) and marine natural plants (MNP). The comparison of the binding energies and the inhibition constants was determined using molecular docking method. Three compounds including two FDA approved (Ibrutinib, Idelalisib) and one MNP (Kumusine) were selected for further investigation using the molecular dynamics simulations. The results indicated that Ibrutinib and Idelalisib are oral medications while Kumusine, with proper hydrophilic and solubility properties, is an appropriate candidate for nsp-16 inhibitor and can be effective to control COVID-19 disease.

Download Full-text

Homology Modeling and Virtual Screening Studies of Antigen MLAA-42 Protein: Identification of Novel Drug Candidates against Leukemia—An In Silico Approach

Computational and Mathematical Methods in Medicine ◽

10.1155/2020/8196147 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Ihsan A. Shehadi ◽

Huda R. M. Rashdan ◽

Aboubakr H. Abdelmonsef

Keyword(s):

Virtual Screening ◽

Homology Modeling ◽

Protein Identification ◽

Binding Affinities ◽

Monocytic Leukemia ◽

Drug Candidates ◽

Promising Target ◽

Leukemia Treatment ◽

Potent Drug ◽

Novel Drug

Monocytic leukemia-associated antigen-42 (MLAA-42) is associated with excessive cell division and progression of leukemia. Thus, human MLAA-42 is considered as a promising target for designing of new lead molecules for leukemia treatment. Herein, the 3D model of the target was generated by homology modeling technique. The model was then evaluated using various cheminformatics servers. Moreover, the virtual screening studies were performed to explore the possible binding patterns of ligand molecules to MLAA’s active site pocket. Thirteen ligand molecules from the ChemBank™ database were identified as they showed good binding affinities, scaffold diversity, and preferential ADME properties which may act as potent drug candidates against leukemia. The study provides the way to identify novel therapeutics with optimal efficacy, targeting MLAA-42.

Download Full-text

Natural Products as Modulators of Sirtuins

Molecules ◽

10.3390/molecules25143287 ◽

2020 ◽

Vol 25 (14) ◽

pp. 3287 ◽

Cited By ~ 2

Author(s):

Berin Karaman Mayack ◽

Wolfgang Sippl ◽

Fidele Ntie-Kang

Keyword(s):

Natural Products ◽

Drug Discovery ◽

Histone Deacetylases ◽

High Throughput Screening ◽

Chemical Space ◽

Class Iii ◽

Drug Candidates ◽

Starting Point ◽

Recent Developments ◽

Potent Drug

Natural products have been used for the treatment of human diseases since ancient history. Over time, due to the lack of precise tools and techniques for the separation, purification, and structural elucidation of active constituents in natural resources there has been a decline in financial support and efforts in characterization of natural products. Advances in the design of chemical compounds and the understanding of their functions is of pharmacological importance for the biomedical field. However, natural products regained attention as sources of novel drug candidates upon recent developments and progress in technology. Natural compounds were shown to bear an inherent ability to bind to biomacromolecules and cover an unparalleled chemical space in comparison to most libraries used for high-throughput screening. Thus, natural products hold a great potential for the drug discovery of new scaffolds for therapeutic targets such as sirtuins. Sirtuins are Class III histone deacetylases that have been linked to many diseases such as Parkinson`s disease, Alzheimer’s disease, type II diabetes, and cancer linked to aging. In this review, we examine the revitalization of interest in natural products for drug discovery and discuss natural product modulators of sirtuins that could serve as a starting point for the development of isoform selective and highly potent drug-like compounds, as well as the potential application of naturally occurring sirtuin inhibitors in human health and those in clinical trials.

Download Full-text

AN OVERVIEW OF COLORECTAL CANCER: IMPLICATION OF TWO MEDICINAL PLANTS IN THEIR TREATMENT

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i7.33287 ◽

2019 ◽

pp. 47-52

Author(s):

JYOTHI BASINI ◽

SIREESHA RAYADURGAM ◽

SWETHA DAKSHINAMURTHY

Keyword(s):

Colorectal Cancer ◽

Side Effects ◽

Medicinal Plants ◽

Development Process ◽

Sedentary Lifestyle ◽

Tumor Development ◽

Therapeutic Agents ◽

Endemic Plant ◽

Natural Origin ◽

Traditional Medicinal Plants

Nowadays, cancer is one of the most common diseases in humans. Among all types, colorectal cancer (CRC) is one of the most serious types diagnosed in men after lung and prostate cancer while in women it occupies the second position after breast cancer worldwide. The risk factors such as obesity, sedentary lifestyle, bad nutritional habits (high in fats and proteins), smoking, and progressive aging are the cause of CRC. The acquisition of abnormal mutations leads to a consisting of many different arrangements of events during the tumor development process. Over the years, different approaches have been employed, in the treatment of cancer. These include chemotherapy, radiotherapy, surgery, and immunotherapy. Chemotherapy is routinely used for cancer treatment, but the toxicity of chemotherapeutics on healthy cells of the human body is obvious. This is the reason for discovering the new, natural origin, substances with potential cytostatic effects and less toxic side effects on the healthy cells. Medicinal plants have a special place in the management of cancer. Numerous cancer research studies have been conducted using traditional medicinal plants to discover new therapeutic agents with fewer side effects. In this review, we are describing two medicinal plants such as Actiniopteris radiata (Sw.) Link (Mayurashikha) and Terminalia pallida Brandis (Tella karaka) (endemic plant) which are available immensely in Chittoor District are used till today by the traditional herbal practitioners, tribal people is near to Talakona forest and Ayurvedic people for various diseases and also for CRC.

Download Full-text