Curcumin has shown pharmacological properties against different phenotypes of various disease models. Different synthetic routes have been employed to develop its numerous derivatives for diverse and improved therapeutic roles. In this study, we have synthesized curcumin derivatives containing isoxazole, pyrazoles, and pyrimidines and then the synthesized molecules were evaluated for their anti-inflammatory and antinociceptive activities in experimental animal models. Acute toxicity of synthesized molecules was evaluated in albino mice by oral administration. Any behavioral and neurological changes were observed at dose of 10 mg/kg body weight.Additionally, cyclooxygenase-2 (COX-2) enzyme inhibition studies were performed through in vitro assays. In vivo anti-inflammatory studies showed that curcumin with pyrimidines was the most potent anti-inflammatory agent which inhibited induced edema from 74.7% to 75.9%. Compounds 7, 9, and 12 exhibited relatively higher prevention of writhing episodes than any other compound with antinociceptive activity of 73.2%, 74.9%, and 71.8%, respectively. This was better than diclofenac sodium (reference drug, 67.1% inhibition). Similarly, COX-2 in vitro inhibition assays results revealed that compound 12 (75.3% inhibition) was the most potent compound.Molecular docking studies of 10, 11, and 12 compounds in human COX-2 binding site revealed the similar binding modes as that of other COX-2-selective inhibitors. K E Y W O R D Santi-inflammatory, COX-2 inhibition, curcumin derivatives, molecular modeling Chemically curcumin is diferuloylmethane which has attracted much attention of medicinal chemists for various diseases and therapeutic agents development. It has shown its pharmacological safety and wide range of biological activities such as antibacterial to anticancer agent [1][2][3][4] . Currently, curcumin is acclaimed to be one of the most widely researched naturally occurring chemopreventive agent which is cytoprotective to healthy human cells [5][6][7] . In spite of important therapeutic application, limited therapeutic utility concerns are associated with curcumin because of its poor absorption and fast metabolism under physiological conditions [8] . Active methylene and keto moiety are believed to be responsible for its rapid metabolism. In order to circumvent the problem of rapid metabolism and to improve its pharmacokinetics profile, several synthetic modifications have been studied on carbonyl and active methylene moiety [9] . In present study, isoxazole, N-substituted pyrazoles, and pyrimidine ring were incorporated in this focused segment of curcumin. Nitrogen heterocyclic moieties such as pyrazoles and pyrimidines containing derivatives gained considerable attention in medicinal chemistry for

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Tylosin is a macrolide antibiotic used as veterinary drug and growth promoter. Attempts were made for hyper production of tylosin by a strain of Streptomyces fradiae NRRL-2702 through irradiation mutagenesis. Ultraviolet (UV) irradiation of wild-type strain caused development of six morphologically altered colony types on agar plates. After screening using Bacillus subtilis bioassay only morphological mutants indicated the production of tylosin. An increase of 2.7+/-0.22-fold in tylosin production (1500mg/l) in case of mutant UV-2 in complex medium was achieved as compared to wild-type strain (550mg/l). Gamma irradiation of mutant UV-2 using (60)Co gave one morphologically altered colony type gamma-1, which gave 2500mg/l tylosin yield in complex medium. Chemically defined media promoted tylosin production upto 3800mg/l. Maximum value of q(p) (3.34mg/gh) was observed by mutant gamma-1 as compared to wild strain (0.81mg/gh). Moreover, UV irradiation associated changes were unstable with loss of tylosin activity whereas mutant gamma-1 displayed high stability on subsequent culturing.

Raman spectroscopy was employed for the characterisation of blood plasma samples from patients at different stages of breast cancer. Blood plasma samples taken from clinically diagnosed breast cancer patients were compared with healthy controls using multivariate data analysis techniques (principal components analysis-PCA) to establishRaman spectral features which can be considered spectral markers of breast cancer development.All the stages of the disease can be differentiated from normal samples. It is also found that stage 2 and 3 are biochemically similar, but can be differentiated from each other by PCA. The Raman spectral data of the stage 4 is found to be biochemically distinct, but very variable between patients.Raman spectral features associated with DNA and proteins were identified, which are exclusive to patient plasma samples. Moreover, there are several other spectral features which are strikingly different in the blood plasma samples of different stages of breast cancer. In order to further explore the potential of Raman spectroscopy as the basis of a minimally invasive screening technique for breast cancer diagnosis and staging, PCA-Factorial Discriminant Analysis (FDA) was employed to classify the Raman spectral datasetsof the blood plasma samples of the breast cancer patients, according to different stages of the disease, yielding promisingly high values of sensitivity and specificity for all stages.

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