Design Synthesis Biological Evaluation and Molecular Modeling Studies of Thiazolidine and related Analogues as Anti HIV 1 Agents

Abstract

ABSTRACT newline newlineCyanobacteria are prominent constituent of ecosystems and account for a significant percentage of marine primary productivity. Due to the exposure to UV radiations they have developed protective strategies to counteract the damaging effects of UV-B. Some species exhibit the ability to produce UV-absorbing compounds (MAAs) under UV-B stress to defend against lethal UV-B damage. newline The realization of the chemical potential of cyanobacteria in recent years has lead to an increase in their applications and products being commercialized. The data from this study can be used to evaluate the potential of cyanobacterium for high MAAs production. If feasible, it can be scaled-up for further study. In this study, unicellular and non-heterocystous cynaobacterium, Synechococcus elongatus PCC 7942 has been used to investigate the effects of UV-B radiation on growth, protein and pigment system. Then, the statistical optimization of nutrient components of BG-11 medium is done for increased production of MAAs using design of experiments. A sequential approach comprising fractional factorial design and central composite design was applied. These studies explored the importance of optimum levels of significant nutrients of the medium used for the production of MAAs. Optimization of media for maximizing the production of MAAs, a potent sunscreen compound, is a captivating study, as MAAs have the reported evidence of possessing photoprotective role, have strong UV absorption maxima (310 nm- 362 nm) and high molar extinction coefficient. Further, the effects of UV B radiation were studied on the antioxidant defense system of the test cyanobacterium. Therefore, to assess the antioxidant potential, DPPH radical scavenging assay, Ferric Reducing Antioxidant Power assay (FRAP) and assay of various antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), ASC-POD were carried out. Hence, the experimental work includes the study of cyanobacteria under UV-B stress as to comprehensively characterize the strain in terms of total antioxidant capacity. The antibacterial activity of Synechococcus spp. PCC 7942 was further studied on five potent skin pathogens. The purpose of the antibacterial study was to relate the inhibitory effects of the cyanobacterial compounds specifically on skin pathogens with the exposure to UV-B radiation as UV protecting compounds are already reported in these organisms. newlineThe investigation of last objective gives an overview of in vitro cytotoxity and free radical scavenging activities of different extracts of Synechococcus spp. PCC 7942 on human skin cell line (HaCaT) exposed to UV-B stress. The present study was undertaken to see the UV-B protective role of the bioactive compounds synthesized by Synechococcus spp. PCC 7942 when grown under UV-B stress on skin cancer cell line. newlineIt was seen that the synthesis of carotenoids and phycocyanin increased in the presence of UV-B stress in Synechococcus spp. PCC 7942. Also, twenty-five fold increase in the content of MAAs was observed in the presence of UV-B after statistically optimizing the media. There were alterations in the antioxidative defense system and antibacterial activity of the cyanobacterium. The extracts of the culture exposed to UV-B stress showed good cytotoxocity and scavenging of reactive oxygen species (ROS) on skin cancer cell line, HaCaT, in MTT and ROS assays. newlineThe UV protecting compounds possess remarkable potential in pharmaceutical and cosmetic industry. The truth that the capability to cultivate cyanobacteria in a controlled in-vitro environment with specific growth and induction requirements, makes them ultimate bio-factory for the production of UV-screening compounds. Hence, these can be used in the development of artificial human sunscreens. Sunscreen use has evidently increased due to growing concern that sun exposure is a primary factor of skin cancer and photoageing. Cyanobacteria can accelerate the mark to fulfill the global demand for bio-sunscreens by replacing them with chemically based counterparts. newline newlineKey words: UV-B radiation, synechococcus elongatus PCC 7942, pigments system, media optimization, antioxidant, antibacterial, cytotoxicity, reactive oxygen species, skin cell line. newline newline