ABSTRACT
In this study, a series of novel compounds based on 5-(5-nitrothiophene-2-yl)-1,3,4-thiadiazole possessing (het) aryl thio pendant at C-2 position of thiadiazole ring is developed and evaluated as antileishmanial agents using MTT colorimetric assay. 10 New compounds containing aryl and heteroaryl derivatives, started from thiophene-2-carbaldehyde in five steps, were synthesized in good to excellent yields and characterized by 1H-NMR, 13C-NMR, and IR spectroscopy. Through the compounds 6a-j, methylimidazole containing derivative 6e was recognized as the most active compound against L. major promastigotes exhibiting IC50 values of 11.2µg/mL and 7.1µg/mL after 24 and 48 h, respectively. This compound is > 4 fold more effective than Glucantime as a standard drug (IC50 = 50 µg/mL after 24 h and 25 µg/mL after 48 h).
ABSTRACT
BACKGROUND AND OBJECTIVE: Aside from direct toxic effects, Sulfur Mustard (SM) induced serum hormone abnormalities may aggravate ocular complaints, including Ocular Surface Discomfort (OSD) (burning, itching, and redness), dry eye sensation, photophobia, blurred vision, foreign body sensation, and pain. The aim of the current study was to investigate the possible association of ocular complaints with serum hormone concentrations in chronic phase of Sulfur Mustard (SM) exposure. METHODS: As a part of Sardasht Iran Cohort Study (SICS), 372 SM-exposed patients and 128 non-exposed participants were enrolled. Ocular complaints and ocular surface biomicroscopic conditions and serum hormones were compared. RESULTS: The exposed with tearing group had significantly higher mean serum levels of testosterone and prolactin (ng/mL) than controls (5.75 vs. 4.75, P=0.031; 11.71 vs. 8.42, P=0.009). The exposed with OSD group had significantly higher mean serum levels of prolactin than controls (12.48 vs. 6.90, P=0.002). The exposed with photophobia group had significantly higher mean serum levels of testosterone than the matched exposed (6.25 vs. 5.65, P=0.013). The exposed with blurred vision group had significantly higher mean serum levels of Thyroglobulin (Tg) (ng/mL) than the matched exposed (65.73 vs. 32.6, P=0.003). CONCLUSION: Higher mean serum levels of testosterone (in exposed with tearing and photophobia) and prolactin (in exposed with tearing and OSD) may play protective roles against SM effects. Higher mean serum levels of Tg may deteriorate the tear film integrity and optical surface, which causes blurred vision. In the chronic phase of SM toxicity, some ocular surface problems are associated with alterations in the serum concentrations of testosterone, prolactin, and Tg.
ABSTRACT
BACKGROUND & OBJECTIVE: Many biochemical features of sulfur mustard (SM) intoxication have remained unknown. So far, the direct association between biochemical parameter changes and ocular problems in patients exposed to SM is not evaluated. The current study aimed at evaluating the associations between the ocular findings in patients with SM intoxication and the changes of serum and blood biochemical parameters. METHODS: In the current study, 372 patients exposed to SM and 128 matched controls were compared concerning the association between their ocular problems and biochemical parameters. Ocular problems include photophobia, ocular surface discomfort (OSD), etc. Biochemical parameters include uric acid, creatinine (Cr), hematocrit (HCT), total, direct and indirect bilirubin, high-density lipoproteins (HDL), alanine aminotransferase (ALT), calcium (Ca), fasting blood sugar (FBS), mean corpuscular hemoglobin concentration (MCHC), etc. RESULTS: The SM-exposed group with photophobia, OSD, tearing, blurred vision, abnormal tear status, and slit-lamp findings had significantly higher mean serum and blood levels of uric acid, Cr, HCT, and total and indirect bilirubin than the controls. The SM-exposed group with photophobia, tearing, ocular pain, blurred vision, bulbar conjunctival and limbal abnormalities had significantly higher mean serum and blood levels of HDL, ALT, Ca, FBS, MCHC, and HDL, indirect and total bilirubin, compared to the control group. CONCLUSION: The association of photophobia with uric acid, OSD and tearing with Cr, photophobia with HDL, ocular pain with Ca, and blurred vision with FBS may be explained for their known ocular effects in the SM-exposed subjects. SM-induced biochemical changes may intensify the ocular problems induced by the direct effects of SM.
ABSTRACT
BACKGROUND: Cutaneous Leishmaniasis (CL) is endemic in many tropical and subtropical regions of the world. Due to the prolonged duration of therapy, adverse effect and resistance to current drugs in the treatment of CL, the discovery of novel, efficient, and safe leishmanicidal drugs is required. The aims of the present study was to synthesis of new compounds based on the active compounds of 5-(5-nitrofuran-2-yl)- and 5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazole bearing the linear amino alcohol of 3-aminopropan-1-ol in the C-2 position of thiadiazole ring and evaluation of their activity against the promastigote and amastigote forms of Leishmania major. METHODS: Reaction between the solution of 5-(5-nitro heteroaryl)-2-chloro-1,3,4-thiadiazole and piperidin-4-ol in absolute ethanol was performed and the resulting products were evaluated against promastigotes form of L. major with MTT assay and amastigote form of L. major in murine peritoneal macrophages. In addition, the toxicity of these compounds was assessed against mouse peritoneal macrophages with MTT assay. RESULTS: New synthetic compounds 5a-b showed moderate in vitro antileishmanial activity against L. major promastigotes with IC50 values of 68.9 and 27µM, respectively. These compounds have also demonstrated a good antiamastigote activity in terms of amastigote number per macrophage, the percentage of macrophage infectivity and infectivity index. CONCLUSION: Novel cyclic compounds 5a-b were synthesized and exhibited less antipromastigote and antiamastigote activity compared to linear analogues.
