اسلامی مملکت کے بین الاقوامی تعلقات عصرحاضر کے تناظر میں

Islam where considers the superiority of law, provision of justice and equity, building and purification of civilization and emphasis on the welfare of society, there ensures the first priority to humanity, peace and prosperity in the external relations. Islamic state keeps relations on the basis of equality with the world and non-Muslim citizens living within the state. On this belief and ideology Islam invites the world to set together. Islam on these principles of Islamic ideology and belief sets the foundation of collectiveness. On this principle the whole philosophy of life and living system are embraced, and the same Islamic law is the foundation of nations, on this behalf the Islamic state organized the relation with other states. In this way Islamic state on these principles keep relations with other states and within the state relations between Muslim and non-Muslim citizens on the basis of brotherhoods, equality, mercy and the principles of dignity of human being. Along with peace Islam set the principles of war which comprise ethical and prison limitations, duties and ethics amongst warrior, difference between the rights of fighters and non-fighters, treatment with pact holders and prisoners, and specified the way of better treatment with the defeated nations. He thought the manners of war to bloody man who consider everything right during the war. Islam lays great stress on equality, social justice, brotherhood and peace not only in state but across the boarders too. In this article a deep study is done to explain the relations of an Islamic state with other states. Islamic foreign policy emphasizes on the principles of equality among all the human beings and all the races and nations. Islam builds international relation on humanitarian basis.

Isolation, Structural Characterization and Docking Studies of Antileishmanial Compound from Endophytic Fungi of Taxus Fuana

Parasitic diseases like leishmaniasis are major worldwide health problem. Suboptimal therapies and emergence of resistance demands the exploration of all possible sources to find a new drug against leishmaniasis. In this search, endophytes have emerged as an outstanding source of high metabolic diversity. These microorganisms have recently attracted increased attention in the quest of pharmaceutically important compounds. Present study describes the biological evaluation of five endophytic fungi Plectania milleri NFL1, Trichoderma asperellum NFL2, Paraconiothyrium sp. NFL6, Mucor hiemalis NFW6 and Epicoccum nigrum NFW7 isolated from Taxus fuana of West Himalayan region of Pakistan followed by isolation and identification of compounds from selected endophytic fungi with prime focus on their antileishmanial activity. Endophytic fungal strains were initially cultivated on four solid state media (PDA, SDA, modified taxol medium and rice) and extracted with organic solvent ethyl acetate. The crude extracts obtained after extraction, were evaluated in phytochemical assays to determine the total phenolic and total flavonoid content. Biological activities of the extracts were determined by three antioxidant assays (total antioxidant capacity, reducing power and DPPH free radical scavenging assay), antibacterial assay against 8 bacterial strains, antileishmanial assay against two Leishmania sp. i.e. L. tropica and L. amazonensis and anticancer assays by evaluating the inhibition of NFƙB and K-Ras. Cytotoxic potential was evaluated against four human cell lines i.e. prostate cancer cell line PC-3, human colon adenocarcinoma cell line HT-29, estrogen receptor negative human breast cancer cell line MDA-MB-231 and breast cancer cell line MCF-7. Endophytic fungi showed variable biological activities with apparent effect of media used for fermentation. The highest amount of gallic acid equivalent phenolic and quercetin equivalent flavonoid content was found in M. hiemalis NFW6 and E. nigrum NFW7. While significant total antioxidant activity, total reducing power and DPPH scavenging activities were also exhibited by these two strains. Noteworthy antimicrobial activities were exhibited by P. milleri NFL1 and Paraconiothyrium sp. NFL6 particularly against S. epidermidis with zone of inhibition of 20 ± 0.87 and 20.7 ± 1.26 mm, respectively. Results for antileishmanial activities were pronounced xiiifor P. milleri NFL1 and M. hiemalis NFW6 against Leishmania sp. with IC 50 values of 1.5 ± 1.1 and 3.72 ± 1.7 μg/ml, respectively. Significant inhibition of NF-κB signaling pathway (>70 %) was exhibited by P. milleri NFL1 and E. nigrum NFW7. Similarly, P. milleri NFL1 and T. asperellum NFL2 showed pronounced K-Ras inhibition (>60 %). Endophytic fungi expressed significant cytotoxic activities against all the cancerous cell lines except human colon adenocarcinoma cell line HT-29. Most promising results were observed against breast cancer cell line MCF-7 where P. milleri NFL1, T. asperellum NFL2 and Paraconiothyrium sp. NFL6 expressed greater than 75 % inhibition. P. milleri NFL1 was the only strain which showed cytotoxic activity against three tested cell lines i.e. PC-3, MCF-7 and MDA-MB-231. Biological screening was followed by selection of P. milleri NFL1, M. hiemalis NFW6 and Paraconiothyrium sp. NFL6 for scale up fermentation and compound isolation. Crude extracts, obtained after the large scale fermentation of endophytic fungi, were fractionated by normal phase chromatography and subjected to antileishmanial assay for prioritizing fractions for compound isolation. Structure elucidation was done by 1D, 2D NMR along with mass spectrometry. As a result, three known compounds were isolated from P. milleri NFL1; pestalotin (L1F5F7F4), its analogue (L1F3F7) and galiellalactone (L1F4F4F4). M. hiemalis NFW6 resulted in the isolation of a single compound i.e. triolein (W6F4F4) while Paraconiothyrium sp. NFL6 also afforded one compound pachybasin (L6F8F14). All the compounds were evaluated for their antileishmanial and anticancer potential. Galiellalactone (L1F4F4F4) was the only compound with antileishmanial and anticancer activity among all the isolated compounds. Antileishmanial potential of galiellalactone has been reported in this study for the first time. In silico tools were employed in this study to understand the behavior of endophytic fungi produced compound galiellalactone (L1F4F4F4) with Leishmania proteins. Thorough study of the literature resulted in selection of three target proteins i.e. leishmanolysin, trypanothione reductase and cysteine protease in Leishmania. These proteins were selected on the basis of their essentiality for Leishmania and absence from human host. Unavailability of experimentally determined structure led to homology modelling of the selected proteins by using eight web-based servers. Comparative analysis was performed to select the most reliable protein model. xivIn silico evaluation of galiellalactone (L1F4F4F4) against leishmanial targets was completed by docking studies. The docking simulation between the ligand (L1F4F4F4) and target proteins was performed using AutoDock. Ligand-protein complex among all the three target protein was most stable in case of cysteine protease with hydrogen bond and electrostatic interactions and highest binding affinity of −6.5 kcal/mol. These findings give insights into possible action of galiellalactone against Leishmania. The Himalayan region of Pakistan has a huge biodiversity of medicinal plants including Taxus species. Antileishmanial potential of endophytes associated with Taxus fuana from this region has not been previously reported. These findings will highlight the bioactive potential of endophytic fungi and also act as a cornerstone for lead compounds for drug discovery and development.