Ajay Sharma

Pharmacological and therapeutic potential of Cordyceps with special reference to Cordycepin

An entomopathogenic fungus, Cordyceps sp. has been known to have numerous pharmacological and therapeutic implications, especially, in terms of human health making it a suitable candidate for ethno-pharmacological use. Main constituent of the extract derived from this fungus comprises a novel bio-metabolite called as Cordycepin (3′deoxyadenosine) which has a very potent anti-cancer, anti-oxidant and anti-inflammatory activities. The current review discusses about the broad spectrum potential of Cordycepin including biological and pharmacological actions in immunological, hepatic, renal, cardiovascular systems as well as an anti-cancer agent. The article also reviews the current efforts to delineate the mechanism of action of Cordycepin in various bio-molecular processes. The study will certainly draw the attention of scientific community to improve the bioactivity and production of Cordycepin for its commercial use in pharmacological and medical fields.

Imidazoles as Promising Scaffolds for Antibacterial Activity: A Review

In the last few decades, a lot of work has been done on heterocycles, especially the imidazole ring, to obtain a scaffold with potential pharmacological properties such as antibacterial, antifungal, anticancer, antiviral, antidiabetic and others, with lesser side effects. The search for new biologically active imidazoles continues to be an interesting area of investigation in medicinal chemistry. The present paper aims to bring together and discuss the wealth of information on antibacterial profile of imidazoles. So it can be employed for future development to obtain new potent drug molecules.

Kaempferol – A dietary anticancer molecule with multiple mechanisms of action: Recent trends and advancements

n Abstractn n The consumption of diet-based naturally bioactive metabolites is preferred to synthetic material in order to avert health-associated disorders. Among the plant-derived polyphenols, kaempferol (KMF) is considered as a valuable functional food ingredient with a broad range of therapeutic applications such as anti-cancer, antioxidant and anti-inflammatory uses. KMF acts on a range of intracellular as well as extracellular targets involved in the cell signaling pathways that in turn are known to regulate the hallmarks of cancer growth progressions like apoptosis, cell cycle, invasion or metastasis, angiogenesis and inflammation. Importantly, the understanding of mechanisms of action of KMF-mediated therapeutic effects may help the scientific community to design novel strategies for the treatment of dreadful diseases. The current review summarizes the various types of molecular targets of KMF in cancer cells as well as other health-associated disorders. In addition, this review also highlights the absorption, metabolism and epidemiological findings.n n

Ursolic Acid and Oleanolic Acid: Pentacyclic Terpenoids with Promising Anti-Inflammatory Activities.

BACKGROUNDnPlant derived products are not only served as dietary components but also used to treat and prevent the inflammatory associated diseases like cancer. Among the natural products pentacyclic terpenoids including ursolic acid and oleanolic acid are considered as the promising anti-inflammatory therapeutic agents.nnnOBJECTIVESnThe current review extensively discusses the anti-inflammatory therapeutic potential of these pentacyclic moieties along with their proposed mechanisms of action. Furthermore, the relevant patents have also been listed to present the health benefits of these promising therapeutic agents to pin down the inflammatory diseases. Expert opinion: Pentacyclic terpenoids are known to negatively down-regulate a variety of extracellular and intracellular molecular targets associated with disease progression. The major anti-inflammatory effects of these molecules have been found to be mediated via inactivation of NFkB, STAT3/6, Akt/mTOR pathways. A number of patents on UA & OA based moieties have been reported between 2010 and 2016. Still there have been only a few compounds which meet the need of sufficient hydro solubility and bioavailability along with higher anti-inflammatory activities. Thus, it is essential to develop novel derivatives of terpenpoids which may not only overcome the solubility issues but also may improve their therapeutic effects. In addition, scientific community may utilize nanotechnology based drug delivery systems so as to increase the bio-availability, selectivity and dosages related problems.

Mechanistic insight into carnosol-mediated pharmacological effects: Recent trends and advancements

&NA; For several decades, bioactive phytochemicals have been appreciated to prevent and cure various lethal diseases. Many studies have proven the ability of dietary phytochemicals to avoid and retard tumor initiation and progression. Among the pharmacologically active moieties, terpenoids are considered one of the most important classes. Carnosol, is also a kind of diterpenoid, which known to possess a range of therapeutic effects such as anti‐cancer, anti‐inflammatory, and anti‐oxidant activities. All these effects are mediated via modulating different signaling cascades, including apoptosis regulating molecules (Bax/Bcl2), prosurvival‐proproliferative molecules (Akt/mTOR, MAPK), transcription factors like NF‐kappaB, STAT3‐6, and steroid receptors, such as androgen and estrogen receptors. The present review highlights the recent trends and advancements have been done in the field of research by using carnosol. Graphical abstract Figure. No caption available.

Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy

&NA; A wide variety of chronic diseases, such as neurodegenerative and cardiovascular disorders, diabetes mellitus, osteoarthtitis, obesity and various cancers, are now being treated with cost effective phytomedicines. Since synthetic medicines are very expensive, concerted efforts are being made in developing and poor countries to discover cost effective medicines for the treatment of non‐communicable diseases (NCDs). Understanding the underlying mechanisms of bioactive medicines from natural sources would not only open incipient avenues for the scientific community and pharmaceutical industry to discover new drug molecules for the therapy of NCDs, but also help to garner knowledge for alternative therapeutic approaches for the management of chronic diseases. Fisetin is a polyphenolic molecule of flavonoids class, and belongs to the bioactive phytochemicals that have potential to block multiple signaling pathways associated with NCDs such as cell division, angiogenesis, metastasis, oxidative stress, and inflammation. The emerging evidence suggests that fisetin may be useful for the prevention and management of several types of human malignancies. Efforts are being made to enhance the bioavailability of fisetin after oral administration to prevent and/or treat cancer of the liver, breast, ovary and other organs. The intent of this review is to highlight the in vitro and in vivo activities of fisetin and to provide up‐to‐date information about the molecular interactions of fisetin with its cellular targets involved in cancer initiation, promotion and progression as well as to focus on strategies underway to increase the bioavailability and reduce the risk of deleterious effects, if any, associated with fisetin administration. Graphical abstract: Figure. No caption available.

Synthesis, docking study, and DNA photocleavage activity of some pyrimidinyl hydrazones and 3-(quinolin-3-yl)-5,7-dimethyl-1,2,4-triazolo[4,3-a]pyrimidine derivatives

In the present study, synthesis of a series of some novel 3-(Quinolin-3-yl)-5,7-dimethyl-1,2,4-triazolo[4,3-a]pyrimidine derivatives (4a–e) has been achieved by oxidative cyclization of new pyrimidinyl hydrazone intermediates (3a–e) using hypervalent iodine reagent(III) under mild conditions. The structures of all synthesized compounds were established on the basis of IR, NMR (1H and 13C), mass spectral data, and elemental analysis. All compounds were evaluated for their DNA photocleavage activity. Compounds 4a, 4b, 4d and 3a–e were found to possess good activity at 40xa0μg/μl concentration and were mainly responsible for the conversion of supercoiled form of DNA into open circular form. Further, docking study was carried out using Molegro Virtual Docker version 2010.4.2.0 using PDB (1AB4) in support of the results obtained.

Therapeutic charm of quercetin and its derivatives: a review of research and patents

Bioactive polyphenolic compounds derived from plants are being utilized for prevention of various chronic diseases including cancer and cardiovascular disorders. Quercetin, a potential poly-phenolic flavonol, found in onions, apples and berries, has been implicated against cancer proliferation, chronic inflammation and various other oxidative manifestations. Evidences suggested that quercetin negatively regulates the numerous crucial signaling pathways associated with life-threatening diseases. Major signaling pathways including NF-κB,xa0MAPK, PI3K-AKT and mTOR are found to be regulated by quercetin. In addition, several patents have reported recently on quercetin derivatives describing wide therapeutic applications such as anticancer/antiproliferatory, antioxidative/antiaging, antiviral, anti-inflammatory, cardioprotective. Present review emphasizes the chemistry and sources of quercetin followed by description of its broad-spectrum therapeutic potential along with proposed mechanisms of action. Furthermore, this review also highlights the important modifications in the basic chemical structure of quercetin in terms of published patents. Insolubility of the bioactive compounds restricts their medicinal importance which could be overcome by modifications in the chemical structure of so-called derivatives. Most of the patents deal with the modifications in chemical structure of quercetin mainly at hydroxyl groups and C-6 and C-7 positions.

Celastrol as a pentacyclic triterpenoid with chemopreventive properties

Celastrol is a highly investigated anticancer moiety. It is a pentacyclic triterpenoid, isolated several decades ago with promising role in chemoprevention. Celastrol has been found to target multiple proinflammatory, angiogenic and metastatic proteins. Inhibition of these targets results in significant reduction of cancer growth, survival and metastasis. This review summarizes the varied molecular targets of celastrol along with insight into the various recently published clinical, preclinical and industrial patents (2011-2017).

Molecular targets of celastrol in cancer: Recent trends and advancements

Despite the advancement in the well-equipped and sophisticated laboratories and facilities, cancer remains to be a major cause of death worldwide. Consequently, further investigation of novel strategies need to be evolved. Since the last few decades, the utilization of phytochemicals is emerging against several human cancers, including lung, breast, colon carcinoma, lymphoma, and other hematological malignancies. Terpenoids are a category of therapeutically active phytochemicals that have been utilized against cancer, cardiovascular and neurodegenerative disorders. Particularly, celastrol, a pentacyclic terpenoid, is well-studied for its variety of pharmacological properties. It is well documented that celastrol can modulate a variety of signaling pathways. Celastrols anti-proliferative role has been found to be associated with its pro-apoptotic (via protein kinase B), anti-angiogenic (via vascular endothelial growth factor and vascular endothelial growth factor receptor), anti-metastatic (via matrix metalloproteinases), and anti-inflammatory (via cytokines and chemokines) activities. This review describes various molecular mechanisms of celastrol for understanding the biology of cancer initiation, progression as well as designing efficacious therapeutic strategies.