Vikas Jaitak

Coumarins as anticancer agents: A review on synthetic strategies, mechanism of action and SAR studies

Coumarins are fused benzene and pyrone ring systems which prompt biological investigation to assess their potential therapeutic significance. It possesses immeasurable anticancer potential with minimum side effects depending on the substitutions on the basic nucleus. Coumarins have a tremendous ability to regulate diverse range of cellular pathways that can be explored for selective anticancer activity. This is the first standalone review that emphasis on the assorted retrosynthetic approaches, important targets for molecularly targeted cancer therapy and structure activity relationship studies that highlight the chemical groups responsible for evoking the anticancer potential of coumarin derivatives reported from 2011 to 2014.

Anticancer activity of essential oils: a review

Natural essential oil constituents play an important role in cancer prevention and treatment. Essential oil constituents from aromatic herbs and dietary plants include monoterpenes, sesquiterpenes, oxygenated monoterpenes, oxygenated sesquiterpenes and phenolics among others. Various mechanisms such antioxidant, antimutagenic and antiproliferative, enhancement of immune function and surveillance, enzyme induction and enhancing detoxification, modulation of multidrug resistance and synergistic mechanism of volatile constituents are responsible for their chemopreventive properties. This review covers the most recent literature to summarize structural categories and molecular anticancer mechanisms of constituents from aromatic herbs and dietary plants.

Chemical composition and antibacterial activity of essential oils of Lantana camara, Ageratum houstonianum and Eupatorium adenophorum.

Essential oils have applications in folk medicine, food preservation, and as feed additives. The essential oils of Lantana camara Linn. (Verbenaceae), Ageratum houstonianum Mill. (Asteraceae) and Eupatorium adenophorum Spreng. (Asteraceae) were analyzed by Gas chromatography-mass spectrometry (GCMS). In L. camara oil, of the total identified (83.91%) volatile constituents, five constituents [3,7,11-trimethyl-1,6,10-dodecatriene (28.86%), β-caryophyllene (12.28%), zingiberene (7.63%), γ-curcumene (7.50%) and α-humulene (3.99%)] represented the major ones. In A. houstonianum oil, among the total identified volatile constituents (94.51%), three [precocene-II (52.64%), precocene-I (22.45%) and β-caryophyllene (9.66%)] represented the major ones. In E. adenophorum oil, of the total identified volatile constituents (84.95%), six [1-napthalenol (17.50%), α-bisabolol (9.53%), bornyl acetate (8.98%), β-bisabolene (6.16%), germacrene-D (5.74%) and α- phellandrene (3.85%)] represented the major ones. The antibacterial activity expressed as Minimum Bactericidal Concentration (MBC) (μg/mL) was determined by the broth dilution method. The essential oil of E. adenophorum had antibacterial activity against Arthrobacter protophormiae, Escherichia coli, Micrococcus luteus, Rhodococcus rhodochrous, and Staphylococcus aureus with MBC values of 200, 100, 100, 12.5, and 200, respectively. The essential oil of A. houstonianum showed antibacterial activity against M. luteus and R. rhodochrous with MBC of 100 and 12.5, but not against A. protophormiae, E. coli, and S. aureus. The essential oil of L. camara showed antibacterial activity against A. protophormiae, M. luteus, R. rhodochrous and S. aureus with MBC of 50, 25, 12.5, and 200, respectively, but not against E. coli. MBC was lowest for R. rhodochrous for all the three essential oils.

Recent developments of C-4 substituted coumarin derivatives as anticancer agents

Cancer is a prominent cause of death in global. Currently, the numbers of drugs that are in clinical practice are having a high prevalence of side effect and multidrug resistance. Researchers have made an attempt to expand a suitable anticancer drug that has no MDR and side effect. Coumarin scaffold became an attractive subject due to their broad spectrum of pharmacological activities. Coumarin derivatives extensively explored for anticancer activities as it possesses minimum side effect along with multi-drug reversal activity. Coumarin derivatives can act by various mechanisms on different tumor cell lines depending on substitution pattern of the core structure of coumarin. Substitution on coumarin nucleus leads to the search for more potent compounds. In this review, we have made an effort to give a synthetic strategy for the preparation of C-4 substituted coumarin derivatives as anticancer agents based on their mechanism of action and also discuss the SAR of the most active compound.

Indole Derivatives as Anticancer Agents for Breast Cancer Therapy: A Review.

Breast cancer (BC) is the second most common cause of cancer-related deaths in women throughout the world. Multiple drugs have been approved by US-FDA for breast related malignancies. Frequent emergence of resistances creates the severe need of newer moieties that are free from such problems. Drugs targeting breast cancer have been observed to be based on the multiple mechanisms of action, and various indole based anticancer agents have also been explored. Moreover, indoles have promising anti-cancer potential; there has been the emphasis on the synthesis of indole derivatives to overcome problems faced by existing therapeutic agents. Taking into consideration the above-mentioned facts we have analyzed in detail the possible role of indole based anticancer agents typically for breast related malignancies. This is the first exhaustive review that jointly covers various synthetic anticancer indole derivatives and related signaling pathways by which these derivatives have shown promising anti-breast cancer potential.

Interaction model of steviol glycosides from Stevia rebaudiana (Bertoni) with sweet taste receptors: A computational approach

Docking studies were performed on natural sweeteners from Stevia rebaudiana by constructing homology models of T1R2 and T1R3 subunits of human sweet taste receptors. Ramachandran plot, PROCHECK results and ERRAT overall quality factor were used to validate the quality of models. Furthermore, docking results of steviol glycosides (SGs) were correlated significantly with data available in the literature which enabled to predict the exact sweetness rank order of SGs. The binding pattern indicated that Asn 44, Ans 52, Ala 345, Pro 343, Ile 352, Gly 346, Gly 47, Ala 354, Ser 336, Thr 326 and Ser 329 are the main interacting amino acid residues in case of T1R2 and Arg 56, Glu 105, Asp 215, Asp 216, Glu 148, Asp 258, Lys 255, Ser 104, Glu 217, Leu 51, Arg 52 for T1R3, respectively. Amino acids interact with SGs mainly by forming hydrogen bonds with the hydroxyl group of glucose moieties. Significant variation in docked poses of all the SGs were found. In this study, we have proposed the mechanism of the sweetness of the SGs in the form of multiple point stimulation model by considering the diverse binding patterns of various SGs, as well as their structural features. It will give further insight in understanding the differences in the quality of taste and will be used to improve the taste of SGs using semi-synthetic approaches.

Impact of ABC transporters, glutathione conjugates in MDR and their modulation by flavonoids: an overview

Overexpression of ATP-binding cassette (ABC) transporter and glutathione conjugates results in efflux of cytotoxic agent from tumor cells leading to multidrug resistance (MDR). Many MDR inhibitors have been identified but none of them have been proven clinically valuable without side effects. Efforts are continue to develop an ideal MDR inhibitor. Recently, herbal modulation of ABC transporter and glutathione conjugates by flavonoids is emerging as popular therapy in MDR. In this review, we have covered structure, function of different ABC transporters and glutathione-mediated MRP overexpression. This review also focuses on the problems with existing MDR inhibitors, modulation of ABC transporter and glutathione-S-transferase by flavonoids.

Molecular docking study of natural alkaloids as multi-targeted hedgehog pathway inhibitors in cancer stem cell therapy

Cancer is responsible for millions of deaths throughout the world every year. Increased understanding as well as advancements in the therapeutic aspect seems suboptimal to restrict the huge deaths associated with cancer. The major cause responsible for this is high resistance as well as relapse rate associated with cancers. Several evidences indicated that cancer stem cells (CSC) are mainly responsible for the resistance and relapses associated with cancer. Furthermore, agents targeting a single protein seem to have higher chances of resistance than multitargeting drugs. According to the concept of network model, partial inhibition of multiple targets is more productive than single hit agents. Thus, by fusing both the premises that CSC and single hit anticancer drugs, both are responsible for cancer related resistances and screened alkaloids for the search of leads having CSC targeting ability as well as the capability to modulating multiple target proteins. The in silico experimental data indicated that emetine and cortistatin have the ability to modulate hedgehog (Hh) pathway by binding to sonic hedgehog (Hh), smoothened (Smo) and Gli protein, involved in maintenance CSCs. Furthermore, solamargine, solasonine and tylophorine are also seems to be good lead molecules targeting towards CSCs by modulating Hh pathway. Except solamargine and solasonine, other best lead molecules also showed acceptable in silico ADME profile. The predicted lead molecules can be suitably modified to get multitargeting CSC targeting agent to get rid of associate resistances.

Chemical Composition and Biological Effects of Artemisia maritima and Artemisia nilagirica Essential Oils from Wild Plants of Western Himalaya

Artemisia species possess pharmacological properties that are used for medical purposes worldwide. In this paper, the essential oils from the aerial parts of Artemisia nilagirica and Artemisia maritima from the western Indian Himalaya region are described. The main compounds analyzed by simultaneous GC/MS and GC/FID were camphor and 1,8-cineole from A.xa0maritima, and camphor and artemisia ketone from A.xa0nilagirica. Additionally, the oils were evaluated for their antibacterial, antifungal, mosquito biting deterrent, and larvicidal activities. A.xa0nilagirica essential oil demonstrated nonselective antifungal activity against plant pathogens Colletotrichum acutatum, Colletotrichum fragariae, and Colletotrichum gloeosporioides, whereas A.xa0maritima did not show antifungal activity. Both Artemisia spp. exhibited considerable mosquito biting deterrence, whereas only A.xa0nilagirica showed larvicidal activity against Aedes aegypti. Antibacterial effects assessed by an agar dilution assay demonstrated greater activity of A.xa0maritima essential oil against Staphylococcus aureus and Pseudomonas aeruginosa compared to A.xa0nilagirica.

Polymeric Encapsulates of Essential Oils and Their Constituents: A Review of Preparation Techniques, Characterization, and Sustainable Release Mechanisms

ABSTRACT Natural polymer based encapsulation of essential oil (EO) is one of the emerging and challenging area of research in perfumery, cosmetics, flavoring agents, preservatives, therapeutics, etc. The knowledge of formulation techniques and physico-chemical properties of the polymers are the basic requirements for the successful encapsulations of essential oils (EOs). This current review article is focused on a comparative account of various formulation techniques based on their applicability. For the first time, it also reviews various physico-chemical techniques used in the analysis of EO encapsulates to determine their stability, structure, surface morphology, and encapsulation efficiency. Further, the mechanisms involved in the release of EOs from encapsulates, along with various factors affecting their release, have also been discussed.