ABSTRACT
BACKGROUND: Compounds possessing urea/thiourea moiety have a wide range of biological properties including anticancer activity. On the other hand, taking advantage of the low toxicity and structural diversity of hydrazone derivatives, they are presently being considered for designing chemical compounds with hydrazone moiety in the field of cancer treatment. With this in mind, a series of novel ureido/thioureido derivatives possessing a hydrazone moiety bearing nitro and chloro substituents (4a-4i) have been designed, synthesized, characterized and evaluated for their in vitro cytotoxic effect on HT-29 human colon carcinoma and HepG2 hepatocarcinoma cell lines. RESULTS: Two compounds (4c and 4e) having the chloro phenylurea group hybridized with phenyl hydrazone bearing nitro or chloro moieties demonstrated potent anticancer effect with the IC50 values between 2.2 and 4.8 µM at 72 h. The mechanism of action of compound 4c was revealed in hepatocellular carcinoma cells as an inducer of apoptosis in a caspase-independent pathway. CONCLUSION: Taken together, the current work presented compound 4c as a potential lead compound in developing future hepatocellular carcinoma chemotherapy drugs. METHODS: The compounds were synthesized and then characterized by physical and spectral data (FT-IR, 1H-NMR, 13C-NMR, Mass). The anticancer activity was assessed using MTT assay, flowcytometry, annexin-V, DAPI staining and Western blot analysis.
ABSTRACT
BACKGROUND: Iranian government has introduced multiple healthcare system reforms during the last 30 years aiming at improving accessibility and affordability of care. Pharmaceutical products are one of the major sources of financial burden on the healthcare system. The healthcare system and pharmaceutical sector have been balanced out by the partially counteracting effects of the HSEP (Health sector evolution plan) and the imposed sanctions. METHODS: This research investigates the healthcare system performance as well as the pharmaceutical market trend mostly based on the financial criteria from 2001. The correlation between the two change patterns was studied to understand the underlying driving market forces. RESULTS: During 2001 to 2013, total health expenditure has grown 25.6% in average. THE (Total health expenditure) share of the GDP remains between 6-7%, while the out of pocket payment has dropped to 37% in 2015 from 57% in 2001, and most health services been directed to the inpatient facilities. Iranian pharmaceutical market has grown rapidly in recent years and grew 28.38% per year and drug consumption per capita reached 34.43$ from 2.28$. However, the import drove most of the market expansion. Noteworthy, the share of pharmaceuticals from THE has also increased. CONCLUSIONS: It is concluded that the sanctions and HSEP have enforced partially counteracting forces on the pharmaceutical market to maintain its consistent growing trend.
ABSTRACT
BACKGROUND: Bacterial resistance to the available antibiotics is a life threatening issue and researchers are trying to find new drugs to overcome this problem. Amongst the different structural classes, thiazolidinone-4-one, as a new effective pharmacophore against various bacteria, has been introduced. OBJECTIVE: A new series of 2-(5-(5-nitrothiophene-2-yl)-1,3,4-thiadiazole-2-ylimino)-5-arylidenethiazolidin- 4-one derivatives were designed and synthesized as new antibacterial agents. METHOD: Target compounds were synthesized during 5 steps and their in vitro antibacterial and anti-H. pylori activities were evaluated. The interaction of the most active derivatives with the probable targets was assessed by Auto Dock 4.2 Program. RESULTS: The results showed that the most potent compounds, 18, 22 and 23, displayed antibacterial activity versus S.aureus, S.epidermidis, B.cereus and B.subtilis (MIC, 1.56-12.5 µg/mL) and none of the derivatives were active on tested Gram-negative bacteria. Compound 12 in all considered doses and compounds 10, and 27 had strong anti-H. pylori activity (inhibition zone >20 mm) in 25 µg disc. Docking studies determined suitable interactions and affinity of potent compounds with bacterial MUR B and H. pylori urease enzymes. CONCLUSION: According to the results most of the derivatives are effective anti-bacterial agents and docking evaluation confirmed their possible mechanisms of actions as MURB and Urease inhibitors.
