Calotropis procera and Calotropis gigantea are medicinal plant having therapeutic value. The leaf extracts of C. procera have been investigated, its pharmacological actions in detail and leaf extracts of C. gigantea were not studied till date. The objective of present work was to find the bioactive constituents present in the ethanolic leaf extract of C. procera and C. gigantea to evaluate their antibacterial and anifungal activities. The major phytochemical groups in C. procera ethanolic leaf extracts were fatty acid ethyl ester (21.36%), palmitic acid ester (10.24%), linoleic acid (7.43%) and amino acid (8.10%) respectively, whereas ethanolic leaf extracts of C. gigantea contain palmitic acid (46.01%), diterpene (26.53%), triterpene (17.39%), linoleic acid (5.13%) as the major phytochemical groups. Ethanol extract of C. procera leaves showed the highest inhibition (11 mm) against Escherichia coli, while ethanolic extract of C. gigantea leaves inhibited Klebsiella (20 mm). These findings will use in new directions in pharmacological investigations.

Cyclooxygenase-2 (COX-2) plays an important role in memory consolidation and synaptic activity, the most fundamental functions of the brain. It converts arachidonic acid to prostaglandin endoperoxide H2. In contrast, if over-expressed, it causes inflammation in response to cytokine, pro-inflammatory molecule, and growth factor. Anti-inflammatory agents, by allosteric or competitive inhibition of COX-2, alleviate the symptoms of inflammation. Coxib family drugs, particularly celecoxib, are the most famous anti-inflammatory agents available in the market showing significant inhibitory effect on COX-2 activity. Due to high cardiovascular risk of this drug group, recent researches are focused on the investigation of new safer drugs for anti-inflammatory diseases. Natural compounds, particularly, phytochemicals are found to be good candidates for drug designing and discovery. In the present study, we performed in silico studies to quantitatively scrutinize the molecular interaction of curcumin and its structural analogs with COX-2, COX-1, FXa and integrin αIIbβIII to investigate their therapeutic potential as a cardiovascular-safe anti-inflammatory medicine (CVSAIM). The results of both ADMET and docking study indicated that out of all the 39 compounds studied, caffeic acid had remarkable interaction with proteins involved in inflammatory response. It was also found to inhibit the proteins that are involved in thrombosis, thereby, having the potential to be developed as therapeutic agent.

The sodium “channelopathies” are the first among the ion channel diseases identified and have attracted widespread clinical and scientific interests. Human voltage gated sodium channels are sites of action of several antiarrhythmic drugs, local anesthetics and related antiepileptic drugs. The present study aims to optimize the activity of Disopyramide, by modification in its structures which may improve the drug action by reducing its side effects. Herein, we have selected Human voltage-gated sodium channel protein type 5 as a potent molecular target. Nearly eighty analogs of Disopyramide are designed and optimized. Thirty are selected for energy minimization using Discovery studio and the LigPrep 2.5. Prior to docking, the active sites of all the proteins are identified. The processing, optimization and minimization of all the proteins is done in Protein preparation wizard. The docking study is performed using the GLIDE. Finally top five ranked lead molecules with better dock scores are identified as having strong binding affinity to 2KAV protein than Disopyramide based on XP G scores. These five leads are further docked with other similar voltage gated sodium channel proteins (PDB IDs: 2KBI, 4DCK, 2L53 and 4DJC) and the best scoring analog with each protein is identified. Drug likeliness and comparative bioactivity analysis for all the analogs is done using QikProp 3.4. Results have shown that the top five lead molecules would have the potential to act as better drugs as compared to Disopyramide and would be of interest as promising starting point for designing compounds against various Sodium channelopathies.

Aromatase, a catalyst in the aromatization reaction of androgens to estrogen, is a member of the cytochrome p450 superfamily, known as monooxygenases. The synthesized estrogen by Aromatase in breast cancer nourishes the cancer cells and assesses the hormonally growing of cancer cells. Therefore, Aromatase is considered as a potential target in treatment of breast cancer. Nowadays, major considerations in drug's selection in the treatment of cancers are shifted to natural sources due to their low toxicity profiles and better therapeutic functionality. In the present study, we have identified the binding modes of various xanthones, dietary supplements obtained from different plant sources, by using of efficient Biocomputational tools. Through docking studies, it is clear that 10 out of 13 ligands showing hydrogen bonds with amino acids like THR 310, PRO 249, ARG 113, GLY 439 and CYS 347. Sameathxanthone A showed highest dock score of-7.96 with the binding energy-38.46 kcal/mol and two hydrogen bonds with LEU 477 and VAL 373. Subsequently, the ADMET properties of compounds have been predicted computationally.

NO donor drugs showed a significant therapeutic effect in the treatment of many diseases, such as arteriopathies, various acute and chronic inflammatory conditions, and several degenerative diseases. NO-releasing anti-inflammatory drugs are the prototypes of a novel class of compounds, combining the pharmacological activities of anti-inflammatory and anti-nociceptive of drugs with those of NO, thus possessing potential therapeutic applications in a great variety of diseases. In this study, we designed and predicted biological activity by targeting cyclooxygenase type 2 (COX-2) and NFkB subunits and pharmacological profiling along with toxicity predictions of various N-aryl piperamides linked via an ester bond to a spacer that is bound to a NO-releasing moiety (-ONO2). The result of absorption, distribution, metabolism and excretion and Docking studies indicated that among 51 designed molecules PA-3 0 K showed the best binding potential in both the substrate and inhibitory binding pocket of the COX-2 enzyme with affinity values of -9.33 and -5.12 for PDB ID 1CVU and 3LN1, respectively, thereby having the potential to be developed as a therapeutic agent. The results of cell viabilities indicated that PA-3 0 k possesses the best cell viability property with respect to its dose (17.33 ng/ml), with 67.76% and 67.93% viable cells for CHME3 and SVG cell lines, respectively.

Herbal remedies and phytochemicals have been used in traditional medicine. Most of the herbs used in human diet have some major effective elements that can affect various pathways in the human body and play a therapeutic role in healing disorders or diseases. Among the inflammatory diseases, worldwide common disorders possess well-known pathways that can be controlled by diet and behavior. There are some well-established targets that are used for anti-inflammatory drugs like cyclooxygenase type 1 and 2 (COX-1 and COX-2), lipoxygenase, prostaglandin D2 receptor, DP1, CRTH2, and so on. In this article, we investigated the role of phytochemicals, extracted from different commonly used spices in the food industry, in preventing or healing the inflammatory disorders. The ability of such bioactives to inhibit COX-2 enzyme has been investigated and compared with marketed selective and nonselective NSAIDs, aspirin and celecoxib. Thereafter, the pharmacokinetic and pharmacodynamic properties of such ingredients have been evaluated for their druggability potential. The results indicated that piperine showed the best ADME (absorption, distribution, metabolism, and excretion) and toxicity profiles among all bioactives. Also, it possessed better affinity value, -7.80518 kcal/mol and energy binding -85.08 kcal/mol, in inhibition of COX-2 with PDB Id: 1CVU rather than other compounds and significantly the higher dock score than aspirin, close to celecoxib. Therefore, piperine has been suggested to be used as the major ingredient in daily diet as a potent anti-inflammatory and anticancer agent.

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