The human population is affected by the wide range of malignant cancers. Several cancer treatment options, including surgery, radiation, chemotherapy, immunotherapy, and others, are available or within our reach. However, the excessive toxic effects that assimilate the negative impact on patients and thus impede progress in cancer treatment have yet to be identified. Recent efforts in the research and development of anticancer drugs derived from natural products have led to the identification of numerous heterocyclic terpenes that inhibit cell proliferation, metastasis, apoptosis, and other mechanisms. The anticancer activity of the terpenoids is quite promising, and it could lead to more opportunities for cancer therapy. The current chapter provides an overview of recent developments in the field of heterocyclic terpenes and their analogues as anticancer compounds. As a result, this provides an overview of the progress made in developing terpenes and analogues as potential anticancer agents, including their synthetic modification, SAR, and action mechanisms. The current studies are hoped to help researchers in increasing their chances of gaining breakthrough insights in the field that can be used in cancer therapeutic practise.

AIM:Terpenes are natural compounds found in several organisms belonging to the animal and plant kingdom, therefore, constitute the largest class of natural products and were a rich reservoir of candidate compounds for drug discovery. The review aims to focus on the extensive potential of the anti-cancer terpenoid components obtained from natural plant species which may lead to the development of a variety of derived terpenoids moieties.METHOD:Literature survey has been carried out to determine the potential of terpenoids.RESULT:The present article provides an overview of the development of the isoprene unit and the generation of the various types of terpenes that exhibits pharmacological potential. The anti-cancer activity of terpenoids appears promising and will potentially open more opportunities for cancer therapy. However, current studies are restricted to descriptive findings and some of them lack mechanistic insights and systematic structure--activity relationship studies. Future efforts into the systematic identification of the targets of terpenoids are believed to increase the chances of gaining breakthrough insights in the field.CONCLUSION:There is still hope that new therapeutic options for the control of cancer and any other painful syndromes will be developed from terpenes, which were proved to be great candidates for cancer therapeutics.

Immunomodulation activity-guided fractionation of ethanol extract of Brugmansia suaveolens leaves was carried out to isolate a novel compound SUPH036-022A (1) by co-culturing the test fraction/compound activated PBMC with MCF7 and A549 cancer cell lines. Assessment of immune markers in PBMC, and analysis of apoptosis markers and cell cycle was carried out for cancer cells. The structure of the isolated compound was elucidated by spectral analysis. Compound 1 enhanced the secretion of immune markers, IL-2 and IFN-γ, from PBMC. Further, compound 1 treated PBMC increased cell death in MCF7 and A549 cell lines and induced ROS production and mitochondrial membrane perturbation, leading to apoptosis. Flow cytometry analysis revealed; compound 1 stimulated PBMC to cause a five-fold increase in cell cycle perturbations in the sub-G1 stage of cancer cells as compared to the negative control. The compound, in the absence of PBMC, only had a weak cytotoxic activity against these cell lines. Thus, compound 1 is a novel lead for immunomodulation-mediated anticancer activity.

The efficient synthesis of novel 2,2-dimethyl-chroman-6-yl pentadienoic acid amides (7a-e) as synthetic piperine analogs has been established by the condensation of 5-(2,2-dimethyl-chroman-6-yl)-4-methyl-penta-2,4-dienoic acid 6 with various aromatic amines. All the synthesized piperine analogs were bioevaluated for their potential as inhibitors of multidrug efflux pump NorA overexpressing Staphylococcus aureus SA 1199B. Out of all the prepared analogs, 5-(2,2-dimethyl-chroman-6-yl)-4-methyl-penta-2,4-dienoic acid ethyl ester 5 and 5-(2,2-Dimethyl-chroman-6-yl)-4-methyl-2E,4E-pentadienoic acid pyrrolidide 7d were found promising. The active compounds were also evaluated for their synergistic effect with ciprofloxacin, whose results substantially increase the activity of ciprofloxacin against both Nora overexpressing and wild type Staphylococcus aureus isolates. Structures of the synthesized compounds have been elucidated on the basis of spectral data (IR, 1H NMR and Mass analysis).

Cancer is possibly one of the most devastating and complex disease and therefore involves chemotherapy as one of the frontline strategies in its therapy. However, expected toxicity and resistance with chemotherapeutic agents encourage us to use the plant derived natural chemotherapeutic sources at the clinical stage of cancer therapy. In view of this strategy, herein new glycosides and isoflavonoids were isolated from Iris kashmiriana Baker and subjected to structure elucidation followed by their biological evaluation. Isolated compounds and their derivatives were purified by the column chromatography and structural identification was made by a combination of various spectroscopic technique vis. UV, IR, 1H NMR, 13C NMR, DEPT, 2-D NMR and mass spectrometry coupled with chemical analysis. Furthermore, an in silico library of isolated isoflavones and its analogues were designed. NF-kappaB (transcription factor that facilitates angiogenesis, inflammation, invasion and metastasis) was selected as a target to evaluate the anticancer and antioxidant activity of isoflavones and its analogues. Designed library of isoflavones and analogues were docked into the active site of NF-kappa B and the most active 15 analogues were selected for synthesis. Finally, all compounds were evaluated for their cytotoxicity against various cell lines and antioxidant activity with different methods that demonstrate their anti-cancer and anti-oxidant potential. The cell cycle specificity of the cytotoxicity was further analyzed by corresponding analysis, using flow cytometer. Most of the compounds exhibit moderate activity, whereas the 5,7,8-trihydroxy-3-(4-methoxyphenyl)-4H-chromen-4-one, 5,7,8-trihydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one, 5,7,8-triacetoxyoxy-3-(4-methoxyphenyl)-4H-chromen-4-one and 6,7-diacetoxyoxy-3-(4-methoxyphenyl)-4H-chromen-4-one showed distinct broad-spectrum anticancer activity with IC50 values ranges between 3.8 and 5.6 μg/mL. Cell cycle analysis indicates that these compounds induced cell cycle arrest at G2/M phase.

The study was undertaken to develop a simplified procedure for the isolation of bioactive isoflavone from Iris kashmiriana, using a direct method of isolation, avoiding the use of chromatographic techniques. The compound was isolated by commercially viable procedure. The extraction of powdered drug (500 g) was done with petroleum ether (60-80) using a Soxhlet apparatus (24 h run). The petroleum ether extract (gums and resins 2.13 g) was obtained and the marc (400 g) was subjected to extraction with 95% methanol using a Soxhlet apparatus (24 h run). The methanolic extract (5 g) was subjected to successive fractionation with toluene, chloroform and ethyl acetate and n-butanol. On the basis of phytochemical analysis, the glycoside was present in n-butanol fraction. The n-butanol fraction (1.5 g) was taken in dried methanol, passed through activated animal charcoal and subjected to acid hydrolysis. The isoflavone (250 mg), was obtained after the usual process of separation. The purity of the compound was checked by analyzing TLC (Thin Layer chromatography) and melting point. Further, the chemical method was used to characterize the compound by shift reagents using UV spectroscopy. The quantitative estimation of isoflavone was done using RP-HPLC and was found to be 98.9% pure. The "previously undescribed" isoflavone was isolated by modifying approach of solvent/solvent extraction, fractionation and acid hydrolysis. The spectroscopic characterization was equaly done by IR, (HNMR)-H-1, (CNMR)-C-13, Mass spectrometry. 98.9% purity was achieved using RP-HPLC with simple solvent (Methanol and Water 55: 45). (c) 2017 The Author(s). Published by Elsevier B.V.

Valeriana waltichii DC, Caprifoliaceae. is used to have anti-ulcer, anti-spasmodic, anti-epileptic, memory enhancer, anti-anxiety, anti-rheumatic, sedative, anti-asthmatic and diuretic activities. V. waltichii is reported to contain valpotriates. valeric acid, valerenic acid, valechlorine, valerianine, resins and alkaloids. Valeric acid, found in V. wallichii appears similar in structure to the neurotransmitter GABA. Valeric acid also acts as an NMDA-receptor antagonist. The aim of present study was to investigate the neuroprotective effect ofV. wallichii containing valeric acid and its possible mechanism of action in amelioration of intracerebroventricular streptozotocin induced neurodegeneration in Wistar rats. The rhizomes of V. wallichii were powdered coarsely and extracted by percolation method using dichloromethane. Wistar rats (220-250g) of either sex were divided into 5 groups, comprising 6 animals each. Valeric acid was isolated from plant extract and characterized using FT-IR. Picrotoxin (2 mg/kg) was used as GABA-A antagonist. Intracerebroventricular streptozotocin administration caused significant (p<0.05) increase in escape latency, retention transfer latency on morris water maze on 17th, 18th, 19th and 20th day and elevated plus maze on 19th and 20th day respectively, as compared to normal untreated rats. Treatment with V. wallichii extract 100 and 200 mg/kg and valeric acid 20 and 40 mg/kg significantly decreased the escape latency and retention transfer latency, as compared to intracerebroventricular-streptozotocin group. Plant extract and valeric acid also decreased the level of lipid peroxidation and restored glutathione level in rat brains. Administration of Picrotoxin significantly reversed the effects produced by plant extract and valeric acid in intracerebroventricular-streptozotocin treated rats. The findings may conclude that valeric acid present in V. wallichii has significant GABAergic effect in amelioration of experimental dementia.

Plant-derived compounds have played very crucial role in the field of anti-cancer drugs. Various important anti-cancer agents like vincristine, vinblastin, camptothecin, paclitaxel and podophyllotoxin have been isolated from the various plant source. Most of the anticancer drugs act on tubulin site. Beauty of these drugs is planar structure because space between a & ß-subunit of tubulin is very less and planar compounds can fit in the gap and bind to ß-Subunit. Several new agents have been found against cancer including combretastatin A4 phosphate, aliphatic esters and lignans. The basic aim of this review is to explore the potential of newly discovered anticancer compounds, from natural resourses, as a lead for anticancer drug development.

OBJECTIVE:This investigation deals with the development and evaluation (in vitro and in vivo) of pH triggered Eudragit-coated chitosan microspheres of curcumin (CUR) for treating ulcerative colitis.METHODS:CUR-loaded chitosan microspheres were initially prepared by emulsion cross linking method followed by coating with Eudragit S-100. The pharmacodynamics of the developed formulation was analyzed in mice by acetic acid induced colitis model.RESULTS:The developed microspheres were of uniform spherical shape with high entrapment efficiency. CUR-chitosan microspheres showed less intense peaks compared to free CUR confirming inclusion of drug within microspheres as revealed by X-ray diffractogram. Uncoated CUR-chitosan microspheres exhibited burst release within initial 4 h while microspheres coated with Eudragit S-100 prevented premature release of CUR and showed controlled release up to 12 h following Higuchi model. In vivo organ biodistribution study showed negligible amount of CUR in stomach and small intestine confirming integrity of microsphere in upper gastrointestinal tract (GIT). In vivo study revealed significant reduction in severity and extent of colonic damage with CUR-loaded microspheres as compared to pure CUR which was further confirmed by histopathological study.CONCLUSION:In vitro and in vivo studies proved the developed formulations as a promising system for pH-dependent delivery of drug to colon in ulcerative colitis.

Zanthoxylum alatum is used in traditional medicinal systems for a number of diseases like diarrhoea, fever, toothache, inflammation, headache, microbial infections, cancer, etc. The aim of the present study was to evaluate the ethyl acetate extract of Zanthoxylum alatum stem bark for its cytotoxic and antioxidant potential and to isolate the bioactive constituent(s). Cytotoxicity of ethyl acetate extract was studied on different cancerous cell lines such as pancreatic, lung, breast and colon cancer using MTT assay. In vitro antioxidant potential was evaluated using DPPH, Nitric Oxide scavenging assay and ferric reducing power assay. The estimation of total phenolic compounds in the extract was determined by Folin-Ciocalteu’s method. Isolation of compounds from ethyl acetate extract was done on silica gel column. Structure elucidation was done by using various spectrophotometric techniques like UV, IR, NMR and MS spectroscopy. All statistical analysis was conducted using Graph Pad Prism software. Ethyl acetate extract of plant has shown significant cytotoxic potential on lung and pancreatic cancer cell lines and also shown antioxidant potential. Flavonoids; apigenin and kaempferol-7-O-glucoside have been isolated from column and has shown significant cytotoxic potential. Flavonoids isolated from ethyl acetate extract were responsible for cytotoxic activity of the extract. Hence the Zanthoxylum alatum can be further explored for the development of anticancer drug.

Introduction: leaves and seed oil of Prinsepia utilis Royle are traditionally used for rheumatism, pain, arthritis, bone disorders and joint ailments. This study was designed to investigate the anti-oxidant effect and anti-osteoporotic potential of Prinsepia utilis Royle in ovariectomized female rats. Methods: Female Wistar rats (180-200 g) were divided into 6 different groups (n = 5 per group). Acute toxicity studies were carried out as per the OECD 423 guideline. Osteoporosis was induced by surgical ovariectomy model. The phytochemical screening and in vitro anti-oxidant activity using DPPH assays of Prinsepia utilis Royle extracts were also carried out. Results: Surgical removal of ovaries caused pathological changes similar to osteoporosis. P. utilis extracts 50, 100 and 200 mg/kg produced a significant increase in bone density, bone strength, alkaline phosphatase activity, serum calcium, serum phosphorous and a decrease in urine hydroxylproline levels, as compared to ovarectomised control rats. The phytochemical screening of P. utilis extract revealed the presence of flavonoids, tannins, terpenoids, beta-sitosterol and ursolic acid. DPPH assay showed prominent free radical scavenging potential of the methanolic extract. Conclusion: The findings suggest that the leaves of the P. utilis Royle have marked protective effect against induced osteoporosis and improved bone quality, attenuated bone resorption, enhanced the rate of bone formation and restored bone density. This may provide evidence for the pharmacological basis for its therapeutic traditional uses. (C) 2014 Elsevier GmbH. All rights reserved.

Abstract Objective: The aim of present investigation was to prepare Curcumin–Zn(II) complex in a view to enhance solubility, stability and pharmacodynamic effect in experimentally induced ulcerative colitis. Method: Curcumin–Zn(II) complex was prepared by stirring curcumin with anhydrous zinc chloride at a molar ratio of 1:1. The prepared curcumin metallocomplex was characterized by TLC, FTIR, UV spectroscopy and 1H NMR. In vitro kinetic degradation and solubility of Curcumin and Curcumin–Zn(II) complex was analyzed spectrophotometrically. Pharmacodynamic evaluation of curcumin and its metal complex was assessed in ulcerative colitis in mice. Results: Curcumin showed chelation with zinc ion as confirmed by the TLC, FTIR, UV spectroscopy and 1H NMR. The results of TLC [Rf value], IR Spectroscopy [shifting of stretching vibrations of υ(C=C) and υ(C=O)], UV spectra [deconvoluted with absorption band at 432–466.4 nm] of Curcumin–Zn(II) complex compared to curcumin confirmed the formation of metallocomplex. 1HNMR spectra of Curcumin–Zn(II) showed the upfield shift of Ha and Hb. Kinetic stability studies showed metallocomplex with zinc exhibited good stability. In vivo study revealed significant reduction in severity and extent of colonic damage with Curcumin–Zn(II) which were further confirmed by histopathological study. Conclusion: This study recognizes higher solubility and stability of Curcumin–Zn(II) complex and suggested better pharmacodynamic effects.

Background: Crotepoxide is a potent molecule for the development of anticancer pharmacodynamics therefore; estimation process for such novel compound is highly desired for future research work in the field of natural products.Introduction: Piper attenuatum is an important species used as a drug in Ayurvedic system of medicine. Pipoxide chlorohydrin, galbelgin, 8-hentriacontanol, several aristolactams, and 4,5-dioxaporphines are the main chemical constituents reported from this plant.Method: Methods based on HPTLC and HPLC with PDA detector for rapid quantitative estimation of crotepoxide in the methanolic extract of Piper attenuatum fruits has been described.Result: The linearity for crotepoxide was found to be in the concentration range of 0.2 to 1.2 mu g/spot with coefficient of determination 0.9988 for HPTLC and 1 to 32 mu g/mL with coefficient of determination 0.9990 for HPLC with respect to peak area. Limit of detection (LOD) and limit of quantification (LOQ) were found to be 60 ng/spot and 198 ng/spot, for HPTLC and 15 ng/mL and 50 ng/mL for HPLC, respectively. Repeatability studies have shown 0.14 % RSD and SE 2.06 for HPTLC and 0.65 % RSD for HPLC. Recovery values of 96.06 to 103.02 % for HPTLC and 98.05 to 100.09 % for HPLC indicate excellent accuracy of the methods.Conclusion: HPTLC and HPLC analyses of the fruit extract had shown percent content of crotepoxide 2.5 and 2.43, respectively, which appears to be the highest from any plant source. The developed methods are accurate, precise, cost-effective, and can be successfully applied for the estimation of crotepoxide.

The present study was aimed to develop and optimize the microsponges of curcumin for colon specific drug delivery in a view to bypass the upper gastrointestinal tract (GIT) for enhanced therapeutic effect. Microsponges were developed by quasi emulsion solvent diffusion method using 32 full factorial design. Prepared microsponges were optimized in order to analyze the effects of independent variables (volume of ethanol and Eudragit L100) on the encapsulation efficiency, particle size, and drug release. The optimized formulation was subjected to in vivo study using acetic acid induced colitis model in rats. The F7 was selected as optimized formulation based on particle size of 41.63 μm, % entrapment efficiency of 78.13%, and % cumulative drug release of 84.12%, and desirability factor of 0.83. Release studies revealed that microsponges prevented the premature release of curcumin in upper GIT and specifically released the drug at colonic pH. The drug release profile of F7 formulation was subjected to different kinetic models and based upon the best correlation coefficient (r2=0.9927) the release was found to follow Higuchi model, which suggested diffusion as the main mechanism of drug release. Pharmacodynamic study showed that curcumin loaded microsponges causes a significant decrease in edema, necrosis, and hemorrhage of colon as compared to free curcumin. This study proves that curcumin loaded microsponges may act as a promising drug delivery system for treatment of ulcerative colitis.

The aim of the present investigation is to develop and statistically optimize the osmotically controlled asymmetric membrane capsules of solid dispersion of lycopene. Solid dispersions of lycopene with β-cyclodextrin in different ratios were prepared using solvent evaporation method. Solubility studies showed that the solid dispersion with 1 : 5 (lycopene : β-cyclodextrin) exhibited optimum solubility (56.25 mg/mL) for osmotic controlled delivery. Asymmetric membrane capsules (AMCs) were prepared on glass mold pins via dip coating method. Membrane characterization by scanning electron microscopy showed inner porous region and outer dense region. Central composite design response surface methodology was applied for the optimization of AMCs. The independent variables were ethyl cellulose (X1), glycerol (X2), and NaCl (X3) which were varied at different levels to analyze the effect on dependent variables (percentage of cumulative drug release (Y1) and correlation coefficient of drug release (Y2)). The effect of independent variables on the response was significantly influential. The F18 was selected as optimized formulation based on percentage of CDR (cumulative drug release) of 85.63% and correlation coefficient of 0.9994. The optimized formulation was subjected to analyze the effect of osmotic pressure and agitational intensity on percentage of CDR. The drug release was independent of agitational intensity but was dependent on osmotic pressure of dissolution medium.

The molecular hybridization (MH) is a strategy of rational design of such ligands or prototypes based on the recognition of pharmacophoric sub-units in the molecular structure of two or more known bioactive derivatives which, through the adequate fusion of these sub-units, lead to the design of new hybrid architectures that maintain pre-selected characteristics of the original templates. The concept of molecular hybridization and the promises/challenges associated with these hybrid molecules along with recent advances on anticancer hybrids and critical discussions on the future aspects of the hybrid drugs have already been presented through a number of reports. However, this article presents the structures of potent hybrids reported during the last two decades along with a detailed account of the patent literature. Significant number of patents on the molecules designed through this valuable drug design technique clearly highlight the present focus of the researchers all around the globe towards hybrid molecules capable of amplifying the effect of individual functionalities through action on another bio target or to interact with multiple targets as one single molecule lowering the risk of drug-drug interactions and minimizing the drug resistance. This review article basically emphasizes the patent literature along with an overview of potent hybrid structures, their IC50 /GI50 values against the various cell lines employed. The present compilation can be utilized as a guide for the medicinal chemists focusing on this area of drug design.

A Hybrid drug which comprises the incorporation of two drug pharmacophores in one single molecule are basically designed to interact with multiple targets or to amplify its effect through action on another bio target as one single molecule or to counterbalance the known side effects associated with the other hybrid part(.) The present review article offers a detailed account of the design strategies employed for the synthesis of anticancer agents via molecular hybridization techniques. Over the years, the researchers have employed this technique to discover some promising chemical architectures displaying significant anticancer profiles. Molecular hybridization as a tool has been particularly utilized for targeting tubulin protein as exemplified through the number of research papers. The microtubule inhibitors such as taxol, colchicine, chalcones, combretasatin, phenstatins and vinca alkaloids have been utilized as one of the functionality of the hybrids and promising results have been obtained in most of the cases with some of the tubulin based hybrids exhibiting anticancer activity at nanomolar level. Linkage with steroids as biological carrier vector for anticancer drugs and the inclusion of pyrrolo [2,1-c] [1,4]benzodiazepines (PBDs), a family of DNA interactive antitumor antibiotics derived from Streptomyces species in hybrid structure based drug design has also emerged as a potential strategy. Various heteroaryl based hybrids in particular isatin and coumarins have also been designed and reported to posses' remarkable inhibitory potential. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the hybrids.