International Conference on Pharmacology and Toxicology October 18-19, 2018 Dubai, UAE

Hamed Felegari is a pharmaceutical student from School of Pharmacy Hamedan University of Medical Sciences-Iran. Member of Student Research Committie, University of Medical Sciences, Hamadan, ‎Iran.

Paraquat is one of the most common herbicides used in agriculture, which can cause very severe toxicity in humans and animals. In this study, we investigated the effect of N-acetyl cysteine and vitamin D on the oxidative toxicity of kidney tissue in sub-acute toxicity with paraquat. 36 male albino rat 8 weeks were randomly divided into 6 groups (n=6). Group 1 or control: Control group (received plate and water), group 2 and 3: Control received with vitamin D dosage in μg/kg/day2 and N-acetyl cysteine 6.25 mg/kg/ day, group 4: Received paraquat 5 mg/kg/day, group 5 and 6: Poisoned with paraquat received vitamin D-treated dose of 2μg/kg/day and N-acetyl cysteine 6.25 mg/kg/day, this treatment continued for 7 days. At the end of the study, serum and kidney tissue collected. Total Antioxidant Capacity (TAC), lipid Peroxidation (LPO), Total Thiol Groups (TTG), urea and creatinine, vitamin D levels in kidney tissue by spectrophotometric and ELISA methods were evaluated. A kidney histo-pathologic evaluation was performed. The value of p<0.05 was considered significant. In paraquat-poisoned groups lipid peroxidation, urea and creatinine were increased and total antioxidant capacity, thiol groups and vitamin D levels decreased significantly (p<0.05). In treated groups, there was a significant decrease in kidney injury, lipid peroxidation, urea and creatinine in comparison with paraquat group and total antioxidant capacity, thiol groups, vitamin D levels significantly increased (P<0.05). Vitamin D decreased oxidative stress and tissue damage in the kidney caused by paraquat poisoning.

Lavinia Berta is working as a Lecturer at General and Inorganic Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy, Tirgu Mures, Romania. Her expertise is in the field of inorganic chemistry-synthesis, identification and characterization of poly-oxometallic compounds (UV-VIS, FT-IR, TGA and ICP). She has two national grants as Principal Investigator. She has many articles published and has participated in many national and international conferences.

Statement of the Problem: Polyoxotungstate are inorganic compounds with a broad range of pharmacological properties (antiviral, antibacterial, anti-tumoral activities). The purpose of this study was to synthesize Na19 [NaAs4 W40O140Pd4 2+] *aq (As4 W40Pd), a new Pd2+ complex of Na27 [NaAs4W40O140] aq (As4W40), a polyoxotungstate cryptand and to assess the antimicrobial activity. Method: The As4 W40 cryptand was synthesized following methods already described in the literature. The complex was obtained by adding PdCl2 solution to As4W40 solution at pH 4, maintaining temperature between 70-80 ºC. After purification the complex was analyzed by spectrometric methods, TGA, conductometry, X-ray diffractometry. The biological activity was studied in vitro on Gram positive and Gram negative bacterial strains by serial dilution method, with identification of Minimum Inhibitory (MIC) and Bactericidal Concentrations (MBC). Findings: The As4W40Pd complex structure is a Leyrie assembly which consist of 4 identical tri lacunar Keggin anion structures ([AsW9 O33]9-) joined together by 4 WO6 octahedra in a ring-like form with high symmetry. The Pd2+ cation is central coordinated inside the structure, in active positions formed in the lacunar places with high electron density. In case of Pd complex a new vibration was noticed at 544 cm-1 corresponding to Pd-O bond. The results obtained by serial dilution method are the following (MIC, MBC=mg/ml): As4W40Pd for Methicillin-resistant Staphylococcus aureus (MRSA, ATCC 44003, Gram positive) MIC=1.48, MBC=1.48; for Pseudomonas aeruginosa (ATCC 27853, Gram negative) MIC=23.69, MBC=23.69; As4 W40-for MRSA MIC=1.00, MBC=1.00 for P. aeruginosa MIC=64.60, MBC=no effect. Conclusion: A new complex was synthesized Na19 [NaAs4 W40O140Pd4 2+]*34H2 O. Both compounds exhibit remarkable antibacterial activity on strains resistant to current therapeutics. The complex was more efficient than the cryptand. MRSA have proved to be more sensitive than P. aeruginosa, which developed resistance to the cryptand. This class of compounds presents biological properties that deserve to be exploited and optimized further more. References 1. Moghayedi M, Goharshadi E K, Ghazvini K, Ahmadzadeh H, Ludwig R, Namayandeh-Jorabchi M (2017) Improving antibacterial activity of phosphomolybdic acid using graphene. Materials Chemistry and Physics; 188: 58-67. 2. Qi W, Qin Y, Qi Y, Guo L, Li J (2015) In vitro antitumor activity of a keggin vanadium-substituted polyoxomolybdate and its ctDNA binding properties. J. Chem.; 2015: 1-6. 3. Grama L, Man A, Muntean DL, Gaz Florea SA, Boda F, Curticapean A (2014) Antibacterial Activity of Some Saturated Polyoxotungstates. Romanian Review of Laboratory Medicine; 22(1): 111-118. 4. Hosseini S M, Amini E, Tavassoti Kheiri M, Mehrbod P, Shahidi M, Zabihi E (2012) Anti-influenza Activity of a Novel Polyoxometalate Derivative (POM-4960). Int. J. Mol. Cell. Med.; 1(1): 21-29. 5. Zhang D, Zhang C, Chen H, Ma P, Wang J, Niu J (2012) Syntheses, structures and properties of dimeric rare earth derivatives based on monovacant Keggin-type polyoxotungstates. Inorganica Chimica Acta; 391: 218-223.

Lingyu Li is a PhD candidate dedicated in structural modification of bioactive natural products. In searching for novel and promising anti-IPF agents, he has achieved a IPF agent library of more than 100 compounds by semisynthetic methods and established a novel rapid IPF agent screening model.

Statement of the Problem: Idiopathic pulmonary fibrosis (IPF) is a severe life-threatening disease with very poor prognosis. IPF patients die within 3 to 5 years after diagnosis mostly due to respiratory failure. To date only 2 small molecule drug (Pirfenidone and Nintedanib) were approved by FDA for IPF treatment, yet they treatment outcome were far from promising. There is an urgent need for novel anti-IPF agents. Methodology & Theoretical Orientation: Matrine and cinnamic acid was rationally hybrid by amidation reactions. An in vitro anti-fibrotic agent screening model was established based on TGF-1 induced human fetal lung fibroblast (MRC-5) myofibroblast transformation. Extracellular total collagen accumulation was quantified by Picro-Sirius Red staining. Transient fibroblast and myofibroblast markers (ACTA2, COL1a1, FSP-1, FAP and P-4-H) expression was determined by immunocytochemistry (ICC) methods. Findings: 46 novel matrine-cinnamic acid hybrid compounds were synthesized and evaluated for their anti-fibrotic activity. 10 ng/mL TGF-1 significantly induces myogenetic phenotype formation with elevated extracellular total collagen accumulation and myofibroblast markers expression. Pretreatment of matrine-cinnamic acid hybrid alleviated TGF-1 induced myogenic transformation. Conclusion & Significance: Compound 3i exhibited an inhibitory effect against TGF-1 induced total collagen accumulation in MRC-5 fibroblast with the IC50 value of 1.2M, which was about 2000 times more potent then Pirfenidone.

Dr. Hai Shang’s research interest focuses on structure modification, activity evaluation and mechanism of action of natural products. He carried out studies on structural optimization of natural pruducts, such as podophyllotoxin, neocrotocembraneic acid and matrine, and found that some derivatives have moderate to good antitumor activity. In addition, a few derivatives of podophyllotoxin and neocrotocembraneic acid exhibited the potential of anti-multidrug resistance by inhibiting the efflux function of P-gp. His research will contribute to the development of novel anticancer drugs with multidrug-resistance modulating potential.

Statement of the Problem: Croton laevigatus Vahl. (Euphorbiaceae) is an arbor that is found mainly in Yunnan, Guangdong, and Hainan Provinces of China. Its roots and leaves have been commonly used as a folk medicine in the Dai nationality of China for the treatment of injury from fall and fracture, malaria and stomachache. In our previous work, we have reported the studies on the chemical composition of the leaves of C. laevigatus Vahl. and seven cembranoids were isolated. The antitumor activity of these compounds were evaluated against HeLa cells and neocrotocembraneic acid showed modest cytotoxic activity. Moreover, this natural product has a high content in C. laevigatus Vahl. (0.7% of the plant’s dry weight) which laid the material foundation for the structural modification. However, there was no study on the structural modification and structure–activity relationship (SAR) of neocrotocembraneic acid related to the antitumor purpose. This stimulated us with great interest to focus on structural modification of neocrotocembraneic acid in order to obtain the initial structure-activity relationship and find novel derivatives with potential antitumor activity. Methodology & Theoretical Orientation: Taking neocrotocembraneic acid as the starting material, the target compounds were synthesized by condensation reaction and click reaction. Their antitumor activities in vitro were evaluated for HeLa, K562 and K562A/02 by MTT. Findings: Eleven novel derivatives were synthesized and the structures were characterized by 1H-NMR、13C-NMR and ESI-MS. MTT assay showed that some cembrane derivatives exhibited antitumor activities. In particular, compounds 2f showed good antitumor activity against HeLa and compounds 2e showed promising antitumor activity against K562 and K562A/02. Conclusion & Significance: Some derivatives have demonstrated promising antitumor activities against K562/A02 cell lines which were worth further studying.