Synthesis and biological activity of structurally diverse phthalazine derivatives: A systematic review

Phthalazine, a structurally and pharmacologically versatile nitrogen-containing heterocycle, has gained more attention from medicinal chemists in the design and synthesis of novel drugs owing to its pharmacological potential. In particular, phthalazine scaffold appeared as a pharmacophoric feature numerous drugs exhibiting pharmacological activities, in particular, antidiabetic, anticancer, antihypertensive, antithrombotic, anti-inflammatory, analgesic, antidepressant and antimicrobial activities. This review presents a summary of updated and detailed information on phthalazine as illustrated in both patented and non-patented literature. The reported literature have described the optimal pharmacological characteristics of phthalazine derivatives and highlighted the applicability of phthalazine, as potent scaffold in drug discovery.     

Drug discovery from medicinal plants

Current research in drug discovery from medicinal plants involves a multifaceted approach combining botanical, phytochemical, biological, and molecular techniques. Medicinal plant drug discovery continues to provide new and important leads against various pharmacological targets including cancer, HIV/AIDS, Alzheimer's, malaria, and pain. Several natural product drugs of plant origin have either recently been introduced to the United States market, including arteether, galantamine, nitisinone, and tiotropium, or are currently involved in late-phase clinical trials. As part of our National Cooperative Drug Discovery Group (NCDDG) research project, numerous compounds from tropical rainforest plant species with potential anticancer activity have been identified. Our group has also isolated several compounds, mainly from edible plant species or plants used as dietary supplements, that may act as chemopreventive agents. Although drug discovery from medicinal plants continues to provide an important source of new drug leads, numerous challenges are encountered including the procurement of plant materials, the selection and implementation of appropriate high-throughput screening bioassays, and the scale-up of active compounds.     

From tradition to innovation: the search for novel therapeutic molecules to treat diabetes

There are over a hundred chemical substances that have been derived from plants for use as drugs and medicines; many more await and medicinal plants are the target of all the attention. The structural diversity of natural products still surpasses that from synthetic compounds and is far beyond any imagination of experts in the field. For many pharmaceutical companies, it is a good argument to investigate natural compounds. Many plants with antidiabetic virtues are known in traditional medicine over the world. The CPID (Centre de Pharmacologie et Innovation dans le Diabète) proposes a technology program to purify new natural antidiabetic substances. A large antidiabetic plant library is constructed for a high-throughput pharmacological screening with cell cultures.     

NeMedPlant: a database of therapeutic applications and chemical constituents of medicinal plants from north-east region of India

The North-East region of India is one of the twelve mega biodiversity region, containing many rare and endangered species. A curated database of medicinal and aromatic plants from the regions called NeMedPlant is developed. The database contains traditional, scientific and medicinal information about plants and their active constituents, obtained from scholarly literature and local sources. The database is cross-linked with major biochemical databases and analytical tools. The integrated database provides resource for investigations into hitherto unexplored medicinal plants and serves to speed up the discovery of natural productsbased drugs. AVAILABILITY: The database is available for free at http://bif.uohyd.ac.in/nemedplant/orhttp://202.41.85.11/nemedplant/     

Recent Updates on Corals from Nephtheidae

Marine natural products display a wide range of biological activities, which play a vital role in the innovation of lead compounds for the drug development. Soft corals have been ranked at the top in regard to the discovery of bioactive metabolites with potential pharmaceutical applications. Many of the isolated cembranoids revealed diverse biological activities, such as anticancer, antidiabetic and anti‐osteoporosis. Likewise, sterols from soft corals exhibited interesting biological potential as anti‐inflammatory, antituberculosis and anticancer. Consequently, investigating marine soft corals will definitely lead to the discovery of a large number of chemically varied secondary metabolites with countless bioactivities for possible applications in medicine and pharmaceutical industry. This review provides a complete survey of all metabolites isolated from the family Nephtheidae, from 2011 until November 2018, along with their natural sources and biological potential whenever possible.     

Rational approaches,design strategies,structure activity relationship and mechanistic insights for therapeutic coumarin hybrids

Hybrid molecules, furnished by combining two or more pharmacophores is an emerging concept in the field of medicinal chemistry and drug discovery that has attracted substantial traction in the past few years. Naturally occurring scaffolds such as coumarins display a wide spectrum of pharmacological activities including anticancer, antibiotic, antidiabetic and others, by acting on multiple targets. In this view, various coumarin-based hybrids possessing diverse medicinal attributes were synthesized in the last five years by conjugating coumarin moiety with other therapeutic pharmacophores. The current review summarizes the recent development (2014 and onwards) of these pharmacologically active coumarin hybrids and demonstrates rationale behind their design, structure-activity relationships (SAR) and mechanistic studies performed on these hybrid molecules. This review will be beneficial for medicinal chemist and chemical biologist, and in general to the drug discovery community and will facilitate the synthesis and development of novel, potent coumarin hybrid molecules serving as lead molecules for the treatment of complex disorders.     

A database for medicinal plants used in the treatment of diabetes and its secondary complications

Effective treatment of diabetes is increasingly dependent on active constituents of medicinal plants capable of controlling hyperglycemia as well as its secondary complications. Sensing the importance of documenting such medicinal plants, here we describe a web database containing information (name, literature citation, active compounds and few related full text articles) of the diabetes medicinal plants exhibiting hypoglycemic, antioxidant and antimicrobial effects. AVAILABILITY: http://www.autogeneralfilters.com/holycross/Home.html.     

Medicinal mushrooms: Valuable biological resources of high exploitation potential

Higher Basidiomycetes and Ascomycetes mushrooms possess various immunological and anticancer properties. They also offer important health benefits and exhibit a broad spectrum of pharmacological activities including antibacterial, antifungal, antiviral, cytotoxic, immunomodulating, anti-inflammatory, antioxidative, antiallergic, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. This minireview summarizes the perspectives, recent advances, and major challenges of medicinal mushrooms with reference to their nutraceutical properties and dietary value, the production of mushroom biomass on various substrates, and the purification, characterization, and pharmaceutical effects of biologically active compounds from medicinal mushrooms.     

Traditional Uses,Chemical Constituents and Biological Activities of Plants from the Genus Thymus

The genus Thymus (Lamiaceae) comprises about 214 species throughout the world, mainly found in North Africa, Europe, and temperate Asia zone. They are traditionally used as food additives and folk medicines. This review comprehensively summarizes information about traditional uses, chemical constituents, and biological activities of this genus and provides recommendations for future investigations. All information was gathered from scientific databases including Google Scholar, Sci‐Finder, Web of Science, ScienceDirect, and CNKI. Volatile oils are the most concerned constituents of this genus. Flavonoids, phenylpropanoids, tannins, organic acids, terpenoids, and phytosterols were also summarized. This genus plants possessed a variety of activities including antimicrobial, antioxidant, anti‐inflammatory, cytotoxic, analgesic, and antidiabetic. In brief, this review will be helpful to provide valuable data for explorations and create more interests towards Thymus genus in the future.     

MPDB 1.0: a medicinal plant database of Bangladesh

The term of medicinal plants include a various types of plants used in herbalism with medicinal activities. These plants are considered as rich resources of ingredients which can be used as complementary and alternative medicines and, also in drug developments and synthesis. In addition, some plants regarded as valuable origin of nutrition. Thus, all these plants are recommended as therapeutic agents. Information related to medicinal plants and herbal drugs accumulated over the ages are scattered and unstructured which make it prudent to develop a curated database for medicinal plants. MPDB 1.0 database is dedicated to provide the first window to find the plants around Bangladesh claimed to have medicinal and/or nutritive values by accumulating data from the published literatures. This database contains 406 medicinal plants with their corresponding scientific, family and local names as well as utilized parts for treatment from different districts of Bangladesh. Information regarding ailments is available for 353 plants. In addition, we have found active compounds for 78 plants with their corresponding PubMed ID.

Availability

www.medicinalplantbd.net     

Medicinal chemistry of indole derivatives: Current to future therapeutic prospectives

Indole is a versatile pharmacophore, a privileged scaffold and an outstanding heterocyclic compound with wide ranges of pharmacological activities due to different mechanisms of action. It is an superlative moiety in drug discovery with the sole property of resembling different structures of the protein. Plenty of research has been taking place in recent years to synthesize and explore the various therapeutic prospectives of this moiety. This review summarizes some of the recent effective chemical synthesis (2014–2018) for indole ring. This review also emphasized on the structure–activity relationship (SAR) to reveal the active pharmacophores of various indole analogues accountable for anticancer, anticonvulsant, antimicrobial, antitubercular, antimalarial, antiviral, antidiabetic and other miscellaneous activities which have been investigated in the last five years. The precise features with motives and framework of each research topic is introduced for helping the medicinal chemists to understand the perspective of the context in a better way. This review will definitely offer the platform for researchers to strategically design diverse novel indole derivatives having different promising pharmacological activities with reduced toxicity and side effects.     

Photosynthetic marine organisms as a source of anticancer compounds

Since early human history, plants have served as the most important source of medicinal natural products, and even in the “synthetic age” the majority of lead compounds for pharmaceutical development remain of plant origin. In the marine realm, algae and seagrasses were amongst the first organisms investigated by marine natural products scientists on their quest for novel pharmaceutical compounds. Forty years after the pioneering work in the field of marine drug discovery began, the biodiversity of marine organisms investigated as potential sources of anticancer, anti-inflammatory, and antibiotic compounds has increased tremendously. Nonetheless, marine plants are still an important source of novel secondary metabolites with interesting biomedical properties. The present review focuses on the antitumour properties of compounds isolated from marine algae, phytoplankton, mangroves, seagrasses, or cordgrasses. Compounds produced by marine epi- or endophytic fungi are also discussed.     

Benzylisoquinoline alkaloid biosynthesis in opium poppy

Opium poppy (Papaver somniferum) is one of the world’s oldest medicinal plants and remains the only commercial source for the narcotic analgesics morphine, codeine and semi-synthetic derivatives such as oxycodone and naltrexone. The plant also produces several other benzylisoquinoline alkaloids with potent pharmacological properties including the vasodilator papaverine, the cough suppressant and potential anticancer drug noscapine and the antimicrobial agent sanguinarine. Opium poppy has served as a model system to investigate the biosynthesis of benzylisoquinoline alkaloids in plants. The application of biochemical and functional genomics has resulted in a recent surge in the discovery of biosynthetic genes involved in the formation of major benzylisoquinoline alkaloids in opium poppy. The availability of extensive biochemical genetic tools and information pertaining to benzylisoquinoline alkaloid metabolism is facilitating the study of a wide range of phenomena including the structural biology of novel catalysts, the genomic organization of biosynthetic genes, the cellular and sub-cellular localization of biosynthetic enzymes and a variety of biotechnological applications. In this review, we highlight recent developments and summarize the frontiers of knowledge regarding the biochemistry, cellular biology and biotechnology of benzylisoquinoline alkaloid biosynthesis in opium poppy.     

Antihyperglycemic activity of compounds isolated from Indian medicinal plants

Eleven antidiabetic Indian medicinal plants were investigated in streptozotocin induced diabetic rat model and provided scientific validation to prove their antihyperglycemic activity. Antidiabetic principles from five plants were isolated. All the compounds isolated were evaluated for antihyperglycemic activity in streptozotocin induced diabetic rat model and activities were compared with standard drug metformin. Some compounds were also screened in db/db mice. Two compounds (PP-1 and PP-2) inhibited significantly the activity of PTPase-1B in an in vitro system. This might be the underlying mechanism of antihyperglycemic activity of these compounds.     

Chalcone derivatives and their antibacterial activities: Current development

The increase in antibiotic resistance due to various factors has encouraged the look for novel compounds which are active against multidrug-resistant pathogens. In this framework, chalcone-based compounds showed a diversity of pharmacological properties, and its derivatives possess a high degree of structural diversity, and it is helpful for the discovery of new therapeutic agents. The growing resistance to antibiotics worldwide has endangered their efficacy. This has led to a surging interest in the discovery of new antibacterial agents. Thus, there is an urgent need for new antibacterial drug candidates with increased strength, new targets, low cost, superior pharmacokinetic properties, and minimum side effects. The present review concluded and focuses on the recent developments in the area of medicinal chemistry to explore the diverse chemical structures of potent antibacterial agents and also describes its structure-activity relationships studies. The various synthetic structures leading to this class of neutral protective compound is common and additional structural optimization is promising for potential drug discovery and development.     

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

The 1,2,3-triazole ring is a major pharmacophore system among nitrogen-containing heterocycles. These five-membered heterocyclic motifs with three nitrogen heteroatoms can be prepared easily using ‘click’ chemistry with copper- or ruthenium-catalysed azide-alkyne cycloaddition reactions. Recently, the ‘linker’ property of 1,2,3-triazoles was demonstrated, and a novel class of 1,2,3-triazole-containing hybrids and conjugates was synthesised and evaluated as lead compounds for diverse biological targets. These lead compounds have been demonstrated as anticancer, antimicrobial, anti-tubercular, antiviral, antidiabetic, antimalarial, anti-leishmanial, and neuroprotective agents. The present review summarises advances in lead compounds of 1,2,3-triazole-containing hybrids, conjugates, and their related heterocycles in medicinal chemistry published in 2018. This review will be useful to scientists in research fields of organic synthesis, medicinal chemistry, phytochemistry, and pharmacology.     

A database for the predicted pharmacophoric features of medicinal compounds

Pharmacophore feature is defined by a set of chemical structure patterns having the active site of drug like molecule. Pharmacophore can be used to assist in building hypothesis about desirable chemical properties in drug molecule and hence it can be used to refine and modify drug candidates. We predicted the pharmacophoric features of 150 medicinal compounds from plants for anti-cancer, anti-carcinogenic, anti-diabetic, anti-microbial, and anti-oxidant. Estimation of pharmacophoric feature is necessary to ensure the optimal supramolecular interaction with a biological target and to trigger or block its biological response. We subsequently make this data available to open access using a database at the URL: http://www.hccbif.info/index.htm AVAILABILITY: The database is available for free at http://www.hccbif.info/index.htm.     

SWEETLEAD: an In Silico Database of Approved Drugs,Regulated Chemicals,and Herbal Isolates for Computer-Aided Drug Discovery

In the face of drastically rising drug discovery costs, strategies promising to reduce development timelines and expenditures are being pursued. Computer-aided virtual screening and repurposing approved drugs are two such strategies that have shown recent success. Herein, we report the creation of a highly-curated in silico database of chemical structures representing approved drugs, chemical isolates from traditional medicinal herbs, and regulated chemicals, termed the SWEETLEAD database. The motivation for SWEETLEAD stems from the observance of conflicting information in publicly available chemical databases and the lack of a highly curated database of chemical structures for the globally approved drugs. A consensus building scheme surveying information from several publicly accessible databases was employed to identify the correct structure for each chemical. Resulting structures are filtered for the active pharmaceutical ingredient, standardized, and differing formulations of the same drug were combined in the final database. The publically available release of SWEETLEAD (https://simtk.org/home/sweetlead) provides an important tool to enable the successful completion of computer-aided repurposing and drug discovery campaigns.