Current Bioactive Compounds - Volume 16, Issue 6, 2020

Background: Piperine, a bioactive alkaloid was a well-known component which was used traditionally to treat a variety of disorders. Objective: The present review is to discuss the modified piperine or piperic acid analogs or its derivatives to explore the potential of piperine. Piperine or piperic acid had potentials as antibacterial, antitumor, antioxidant, anti-inflammatory, antifungal, immunomodulatory and many more for drug development. So modification in natural molecule piperine generates numerous derivatives or analogues which may be found beneficial in drug development. Methods: A literature survey has been carried out to determine the real potential of piperine and its modified analogs. Results: It has been scrutinized that piperine and its derivatives possess valuable components with good therapeutic potential. Conclusion: Thus, this review aims to provide knowledge as well as to explore the excellent potential of piperine, piperic acid, piperine derived compounds/ analogs which may further, after performing toxicity studies, and other parameters, be helpful in the design and development of novel drug candidates against numerous disease conditions and thus it paves way for further work in exploring the potential to treat the patients with obesity and skin related disorders.

The current review focuses on the comprehensive studies of platinum-based complexes that are known to exhibit anticancer properties. The research on metal-particle work has helped in treating sicknesses which plays an imperative part in therapeutic bioinorganic science. Understanding the biochemistry of the detoxification mechanism of metals can help in advancing as well as enhancing the anticancer property of metal complexes for several types of a tumour. The classifications of complexes discussed have been done on the basis of Platinum oxidation states and binding sites of the ligands. Further background and current status of Pt(IV) complexes are briefly explained along with a special reference to Structural Activity Relationships and Mode of Action. The coordination chemistry of Pt(IV) has been summarised and Pt(IV) complexes are reviewed on the basis of binding of Pt(IV) with Human Serum Albumin and DNA. Finally, the results were summarized and concluded emphasizing on the most important features.

Background: This review aims to highlight biotechnological techniques applied for the identification, isolation and propagation of mistletoe-derived bioactive compounds and the preclinical evaluation of their anticancer properties. Methods: We undertook a structured search of bibliographic databases to identify and evaluate the literature, regarding biotechnology of mistletoe and malignancy treatment. The selected articles were classified into five modules according to the study design. Results: Firstly, we have provided an overview of the role of biotechnology in plant-derived pharmaceuticals, by reviewing twelve articles. Then, V. album L. botany and a retrospection of the plant pharmaceutical applications are presented from a set of ten articles. Subsequently, mistletoe derived compounds and their anticancer properties are highlighted, throughout sixty-two articles, which emphasized the mechanisms of antitumor action. The next module is referred to as the biosynthesis of mistletoe bioactive compounds, covering nine cases of ‘in vitro’ propagation and genetic manipulation. Finally, fourteen assays regarding mistletoe preparations and preclinical testing for chemosensitivity are presented. Conclusion: Biotechnology provides essential tools for the identification, production and evaluation of anticancer compounds derived from Viscum album L. The preclinical studies indicate the potential use of V. album preparations in chemotherapy but further research is essential for standardizing the therapeutic benefits of mistletoe compounds in the treatment of malignancies.

Background: Naturally occurring chalcones afford diverse pharmacological activities such as anticancer, anti-malarial, anti-inflammatory, anti-tubercular, anti-hypertensive, anti-arrhythmic, antidiabetic, anti-angiogenic, anti-obesity, antiplatelet, anti-oxidant, hypolipidemic and anti-gout. They are frequently being used by the various researchers to design and develop new synthetic chalcones and many novel hybrid analogs as bioactive drugs. Many of these drugs are hybrid molecules, which are designed through molecular hybridization theory, and have displayed multiple pharmacological and medicinal aspects. This multi-effective feature of these hybrid derivatives makes them efficient and ideal drug entities for the treatment of various dreadful diseases. Methods: A structured search of published research literature from recognized standard medical databases such as PubMed, Google Scholar, Google Patents, Scopus, etc., over the defined period of 10 years (January 2009 to December 2018) have been performed. Various reported heterocyclic chalcone hybrids, their synthesis methods, plausible mechanism(s) of action(s), and probable structure-activity relationships for the therapeutic applications in cancer, malaria, tuberculosis, leishmaniasis, inflammation, diabetes, microbial infection, and cardiovascular diseases remained the centre for attraction of this article. Results: The present review article focuses on chalcone hybrids with different heterocyclic moieties and categorizing them on the basis of their pharmacology and therapeutic significance in the last ten years and has proposed their structure-activity relationships. Conclusion: Chalcone and their hybrids have largely been targeted for their anticancer, anti-malarial, anti-inflammatory, anti-tubercular, antileishmaniasis, and anti-microbial activity. This comprehensive study may assist the medicinal chemist to design and develop innovative chalcone hybrids with significant therapeutic activity.

Background: Polyphenolics, a group of natural substances with a wide distribution in the plant kingdom present a great diversity of biological activities such as anti-oxidative, anti-inflammatory, anti-mutagenic, anti-carcinogenic, modulation of enzyme activity, prevention of CHD, etc. The objective of this review was to describe the relevant aspects of polyphenolics, reporting the different known groups, the probable mechanisms by which they act as anti-inflammatory agents. An attempt was also made to enumerate the possible leads e.g. curcumin, resveratrol, baicalein for further development. Methods: For peer-reviewed research literature we undertook a structured search of bibliographic databases using a focused review question. The quality of retrieved papers was appraised using standard tools. The systemic review consists of research using scientific databases such as PubMed, Scopus, Science Direct, and Google Scholar. Research: Compounds like Quercetin, luteolin, apigenin, fisetin, wogonin, and baicalein showed antiinflammatory activity in-vitro through different cellular mechanisms and these were also reported to possess significant anti-inflammatory activity in animal models of inflammation. Conclusion: It is evident that polyphenolic compounds such as flavonoids, lignans, phloroglucinols, stilbenes, diarylheptanoids, quinones, and phenylpropanoids exhibited significant anti-inflammatory activity in-vivo as well as in-vitro. Although, these active compounds are not drugs per se, however, they deserve further investigation as potential candidates for anti-inflammatory drug development through preclinical and clinical studies.

Background: Coumarins were reported to possess antimicrobial, antiinflammatory, antiplasmodial, antimalarial, and enzyme inhibitory properties. Furthermore, coumarins are a type of vitamin K antagonists. Coumarins had been first organized through perkin reaction; besides Knoevenagel condensation was mentioned as a critical synthetic approach for the synthesis of 3-substituted coumarins. Moreover, Pechmann, Reformatasky and Witting reactions were stated for the preparation of coumarins. Methods: We undertook a structured search of the method of preparation, the chemical reactivity and biological properties that are associated with coumarins and their analogous. Results: Coumarins display a wide range of Src Kinase and cholinesterase inhibitor activities and application of coumarins as antidiabetic, antipsychotic and antiproliferative agents has been addressed. Other properties of coumarins such as their role in antitumor, anticancer, and as antioxidants have also been reviewed. Conclusion: This review concluded that coumarin ring was mixed with other rings, a synergistic effect for each of the ring in their biological activities was obtained, such compounds were exploited to improve various important molecules which provide scaffolds for drug improvement. These compounds were used to broaden a special molecule that gives scaffolds for drug improvement.

Background: As coumarin derivatives are known to prevent and treat various diseases, they have attracted the attention of medicinal chemists. They have strong potential as drugs because their benzopyrone structure can interact noncovalently with numerous enzymes and receptors. Methods: The aim of this review was to summarize the most recently published literature on coumarin derivatives in terms of their antioxidant, antimicrobial, anti-inflammatory, anticancer, and other miscellaneous properties. Results: Coumarin derivatives have a wide range of biological activities. They exhibit antioxidant, antimicrobial, anti-inflammatory, anticancer, anti-coagulant, and anti-Alzheimer effects. Conclusion: The coumarin nucleus is an interesting starting point for the design and development of novel bioactive agents. The present review may help medicinal chemists design biologically active molecules based on the coumarin nucleus.

Background: The primary objective of any pharmacotherapeutics approach entirely lies with the effectiveness of the rationally designed delivery system to effectually deliver the suitable drug at the appropriate concentration at the proper site. Phytosomes are most effective carrier for the possible enhancement of bioavailability, reduction in the clearance rate, providing higher dissolution, and amplification of solubility by several folds of various natural products. Methods: The present review article focuses exclusively on the recent global advancements in the emerging novel drug delivery field of phytosomes from the year 1996 to present. Results: The article comprehensively highlights the reported phospholipid complexes of the active phytoconstituents (18β-Glycyrrhetinic acid, Andrographolide, Baicalein, Baicalin, Berberine, Catechin, Celastrol, Curcumin, Epigallocatechin-3-O-gallate, Evodiamine, Gingerol, Gymnemic acid, Icaritin, Kaempferol, L-carnosine, Luteolin, Mitomycin-C, Piperine, Quercetin, Resveratrol, Rutin, Salicin, Silibinin or Silybin or Silymarin, Sinigrin, and Umbelliferone) and herbal extracts (Aegle marmelos, Allium cepa, Allium sativum, Bacopa monnieri, Boswellia serrata, Butea monosperma, Calendula officinalis, Centella asiatica, Citrullus colocynthis, Ginkgo biloba, Glycine max, Lawsonia inermis, Mentha pulegium, Momordica balsamina, Momordica dioica, Phyllanthus amarus, Phyllanthus emblica, Tecomella undulate, and Woodfordia fruticosa) in treatment of various ailments along with the possible enhancement of pharmacodynamics and pharmacokinetic attributes. The review also exhaustively focuses on the clinical trials of several vesicular products and patents information. Conclusion: This article will be vital for the researchers of numerous fields who are working towards the development of novel drug delivery system for translating better therapeutic effects of herbal based components.

Background: Bacteria communicate by producing small signaling molecules to maintain threshold cell density. Quorum sensing inhibition is an effective and most potent approach for the prevention of cell to cell communication. Methods: In the present study, the methanol extract of Garcinia indica was tested for anti-quorum sensing activity using Chromobacterium violaceum as a biosensor. The extract inhibited violacein production in biosensor strain without affecting the growth of the bacteria and this was corroborated by bioautography assay. Results: The bioactive fraction was analysed by the aid of GC-MS revealed that, the presence of coumarin (7-hydroxy-3-(1,1-dimethylprop-2-enyl) coumarin) and eugenol (1,2-dimethoxy-4-(1-methoxy-1- propenyl) benzene) derivatives as anti-quorum sensing molecules. Conclusion: A detailed investigation is required to study the mechanism of action involved in control of quorum sensing signals and possible applications.

Background: In the present study, chalcones were synthesized from 2-hydroxy-1- acetonaphthone and substituted aromatic aldehydes were synthesized by Claisen Schmidt condensation reaction using potassium hydroxide as a base. The synthesized chalcones were purified by recrystallization from ethanol and evaluated for antibacterial activity by well diffusion method. The antibacterial activity was evaluated against Bacillus licheniformis, Bacillus species, Escherichia coli and Staphylococcus aureus using Ciprofloxacin as a standard. Methods: The target molecules were prepared by reacting 2-hydroxy-1-acetonaphthone and various substituted aromatic aldehyde in the presence of suitable condensing agents. The structure of synthesized compounds was confirmed on the basis of elemental analysis, IR, 1H NMR and 13C NMR spectral data. These synthesized compounds were also screened for antibacterial activity. Results: In the present study, free hydroxyl group in position 2 or 4 of aldehyde ring of synthesized chalcones appears to be a very important requirement in increasing the activity (2-5 and 8-13). When the hydroxyl group in position 4 is alkylated (14, 15), the chalcones become less active. When more complex substituent is present on the aldehyde ring (6, 7) there is a decrease in the activity. Conclusion: Newly synthesized chalcones (1-15) show good and moderate antibacterial activity. We believe that the new hydroxy substituted (in aldehyde ring) chalcones (2-5 and 8-13) reported in this work may provide an interesting insight for further optimization.

Background: Quinoxaline, a fused heterocycle of benzene and pyrazine rings are becoming recognized as a potent class of anti-cancer compounds, such as, in a wide array of pharmacological activities. Methods: We evaluate the three gallate quinoxalines (G-A1, G-A2, and G-A3) as c-Met kinase inhibitors using a docking study, in vitro anticancer potential measurements, antioxidant and bactericidal activities. Results: The docking study showed hydrogen bond linkage of quinoxalines with amino acids at active site of c-Met kinase structures, indicating a possible cancer inhibition cell proliferation. Therefore, the three quinoxalines were analyzed against four in vitro cancer cell lines, and G-A1 demonstrated cytotoxicity against HL-60 and HCT116 cell lines (IC50= 9.55 and IC50= 16.67 μmol L-1, respectively). In HepG2 and MCF-7 cells, the IC50 were 22.48 and 33.42 μmol L-1, respectively. For G-A2 and G-A3, cytotoxic activity ranged from 61.22 to >101.21 μmol L-1. Potent antioxidant activities were also obtained for G-A2>G-A1>G-A3 (IC50= 4.5-8.4 μmol L-1 and AAI= 8.8-17.8). Six different Bacillius strains showed growth inhibition (11.33 to 13.33 mm) in the presence of quinoxaline G-A1 (500 μg). Conclusion: The present work showed the biological potential of quinoxalines G-A1, G-A2 and G-A3 in inhibiting four cancer cells proliferation, in addition to a very strong antioxidant activity.

Background: Pyrimidinones and its derivatives are present in many anti-cancer agents. It has been reported that these substances were proven to have significant activities against different types of human cancers. The incorporation of [1,2,3]-triazole, a nitrogen-rich unit not only increases the efficacy but also increases the lipophilicity of the drug molecule. As our research was to synthesize newer molecules of effective cytotoxicity, we focused on pyrimidinone and [1,2,3]-triazoles systems, as important scaffolds with the expectation of potential cytotoxic properties. Methods: Novel series of [1,2,3]-triazole carboxamides (5a-j) were synthesized, starting from 3-(2- chloroethyl)-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one. The structure of all the synthesized compounds was elucidated based on IR, 1H-NMR, 13C-NMR and LC-MS data. Compounds were focused for their in vitro cytotoxicity against A375 melanoma cancer cell lines, MDA-MB-231 breast cancer cell lines and HEK 293-Human embryonic kidney cell lines using colorimetric MTT assay. The potent compound was evaluated for the DNA binding studies. Results: Most of the Pyrimidinone conjugated [1,2,3]-triazole carboxamides found to be selective towards melanoma cancer cell lines than breast cancer cell lines. Compounds 5d, 5i and 5b were effective against A375 cancer cell lines and are found to be non-toxic against HEK 293-Human embryonic kidney cell lines. The potent compound 5d showed good intrinsic binding constant (Kb) value 3.12 x 103 M-1 in UV based DNA titration. Conclusion: Newly synthesized Pyrimidinone conjugated [1,2,3]-triazole carboxamide derivatives showed the significant cytotoxicity and the potent compound showed good intrinsic binding constant in UV based DNA titration.

Background: Improvement in extract quality in terms of concentration of secondary metabolites and pharmacological activity has always been the need of the hour. In the present research, the target was to extract the selected medicinal herb using the ultrasound waves and to optimize the extraction conditions for the improvement in the quality of extract with respect to furan labdane diterpene (marrubiin) concentration and antihypertensive potential. Methods: The whole plant of Marrubium vulgare Linn. was collected from the fields of Pulwama district of Jammu and Kashmir state in India and extracted by cold maceration (MVM) and ultrasound assisted extraction techniques (MVU). The response surface methodology coupled with the central composite design was employed to optimize the selected extraction parameters in UAE method. The marrubiin concentration in different extracts was determined by HPTLC. The extracts were also evaluated for the antihypertensive potential by non-invasive blood pressure monitoring (NIBPM) method. Results: The extract yield (14.2 ± 0.9%) and concentration of marrubiin (0.91 ± 0.04%) were significantly improved at the optimized UAE conditions (Ultrasound power 467 W, sonication time of 47 minutes and solvent concentration of 33 mL per g of drug) as compared to the conventional method. Furthermore, the MVU extract (200 mg/kg) along with ethanol significantly (p<0.01) prevented the rise in mean systolic blood pressure (MSBP) of animals and also the GSH was significantly (p<0.05) enhanced as compared to ethanol-treated animals. Conclusion: The elevation in MSBP and decrease in reduced glutathione concentration (GSH) by the chronic ethanol consumption were significantly altered by MVU extract as compared to MVM extract. The enhanced antihypertensive effect of selected herb may be attributed to the improved concentration of secondary metabolites (marrubiin) in MVU extract obtained at optimized conditions.

Background: Vector-borne diseases are quite prevalent globally and are one of the major causes of deaths due to infectious diseases. There is an availability of synthetic insecticides, however, their excessive and indiscriminate use have resulted in the emergence of resistant varieties of insects. Thus, a search for novel biopesticide has become inevitable. Methods: Rotenoids were isolated and identified from different parts of Medicago sativa L. This group of metabolites was also identified in the callus culture, and the rotenoid content was monitored during subculturing for a period of 10 months. Enhancement of the rotenoid content was evaluated by feeding precursors in a tissue culture medium. Results: Four rotenoids (elliptone, deguelin, rotenone and Dehydrorotenone) were identified, which were confirmed using spectral and chromatographic techniques. The maximum rotenoid content was found in the seeds (0.33±0.01%), followed by roots (0.31±0.01%) and minimum in the aerial parts (0.20±0.05%). A gradual decrease in the rotenoid content was observed with the ageing of subcultured tissue maintained for 10 months. The production of rotenoids was enhanced up to 2 folds in the callus culture using amino acids, Phenylalanine and Methionine as precursors as compared to the control. The LC50 value of the rotenoids was found to be 91 ppm and 162 ppm against disease vectors of malaria and Dracunculiasis, respectively. Conclusion: The study projects M. sativa as a novel source of biopesticide against the disease vectors of malaria and Dracunculiasis. The use of precursors to enhance the rotenoid content in vitro can be an effective venture from a commercial point of view.