2-(Nitroaryl)-5-substituted-1,3,4-thiadiazole derivatives with antiprotozoal activities: in vitro and in vivo study

Nitro-containing compounds are a well-known class of anti-infective agents, especially in the field of anti-parasitic drug discovery. HAT or sleeping sickness is a neglected tropical disease caused by a protozoan parasite, Trypanosoma brucei. Following the approval of fexinidazole as the first oral treatment for both stages of T. b. gambiense HAT, there is an increased interest in developing new nitro-containing compounds against parasitic diseases. In our previous projects, we synthesized several megazole derivatives that presented high activity against Leishmania major promastigotes. Here, we screened and evaluated their trypanocidal activity. Most of the compounds showed submicromolar IC50 against the BSF form of T. b. rhodesiense (STIB 900). To the best of our knowledge, compound 18c is one of the most potent nitro-containing agents reported against HAT in vitro. Compound 18g revealed an acceptable cure rate in the acute mouse model of HAT, accompanied with noteworthy in vitro activity against T. brucei, T. cruzi, and L. donovani. Taken together, these results suggest that these compounds are promising candidates to evaluate their pharmacokinetic and biological profiles in the futu

Syntheses of substituted-pyrrolo-[2,3-d] imidazoles and substituted-pyrrolo[3,2-d]imidazoles

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Synthesis and Biological Evaluation of 2-Phenyl Benzothiazole Derivatives as Cytotoxic Agents

Cancer is a leading cause of death worldwide. Many heterocyclic cores are present in the structures of clinically approved anticancer drugs. Meanwhile, benzothiazoles have been reported as one of the most important heterocyclic scaffolds in previously reported anticancer agents in the literature. Therefore, in this report, a novel series of 2-phenyl benzothiazole derivatives was synthesized, biologically evaluated against breast cancer cell line (T47D) and compared with etoposide as a reference drug.  The anticancer activities were evaluated by MTT colorimetric assay. Among all tested compounds, N-(4-(6-methoxybenzo[d]thiazol-2-yl)phenyl)acetamide illustrated the most potent cytotoxic activity

Protective effect of pentoxifylline on male wistar rat testicular germ cell apoptosis induced by 3,4-methylenedioxymeth amphetamine

Objective(s): 3, 4-methylenedioxymethamphetamine (MDMA) one of the methamphetamine derivatives that affect the reproductive system, has not been well understood. Many young people are consumers of drugs such as MDMA that can affect their reproductive capability. Apoptosis is the main mechanism for male infertility. Pentoxifylline (PTX) increases cAMP intracellularly and reduces tumor necrosis factor-α. This study aimed to investigate the protective effect of PTX administration in MDMA-induced apoptosis in testes of male Wistar rats. Materials and Methods: Thirty male Wistar rats weighing 250-300 g were randomly divided into five groups: control group (without any intervention), group receiving 7.5 mg/kg MDMA three times every two hours for one day, first experimental group receiving 100 mg/kg PTX just at the time of third injection of MDMA, second experimental group receiving 100 mg/kg PTX a week before MDMA administration, and the vehicle group, which received MDMA+saline. Two weeks later, testes were removed and prepared for H&E staining, TUNEL and Western blot techniques. Results: There was a significant decrease of the score in the MDMA group compared with the control group. In first and second experimental groups, the quality of seminiferous epithelium was improved compared with the MDMA group. The number of TUNEL-positive cells/tubule increased in MDMA and vehicle groups, which is decreased by administration of PTX before MDMA. Expression of active caspase-3 significantly increased in MDMA group, which is significantly decreased by administration of PTX before MDMA. Conclusion: PTX can significantly reduce the severity of lesions in the testes following administration of MDMA. © 2016, Mashhad University of Medical Sciences. All rights reserved

Novel Levofloxacin Derivatives as Potent Antibacterial Agents

In this report, a new series of fluoroquinolone agents which was derived from levofloxacin was synthesized and evaluated against Gram-positive (Bacillus subtillis, Staphylococcus aureus, Staphylococcus epidermidis and Micrococcus luteus) and Gram-negative (Esherichio coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Serratia marcescens) organisms. The results showed that some of the synthesized compounds are strong antibacterial agents. All the synthesized compounds showed remarkable activities against Staphylococcus epidermidis and Staphylococcus aureus (MIC = 0.03-1 µg/mL and 0.06-1 µg/mL respectively)

Synthesis and in vitro Anti-Bacterial Activity of 2-(5-Nitro-2-heteroaryl)-1,3,4-Thiadiazole Derivatives

A new series of 2-(5-nitro-2-heteroaryl)-1,3,4-thiadiazole derivatives, including nitro furan, nitro thiophene and nitro imidazole, were synthesized and screened in vitro for their inhibitory activity against eight bacterial strains. The results showed that most of the synthesized compounds were active against Gram-positive bacteria, determined by MIC method. Among them, compounds 6a, 6b and 6d exhibited strong anti-bacterial effects against the Gram-positive bacteria. The oxidation of synthesized compounds to sulfinyl and sulfonyl bearing analogues did not improve the activity

Spectroscopic and Molecular Docking Studies on DNA Binding Interaction of Podophyllotoxin

The binding interaction of novel podophyllotoxin derivative, (3R,4R)-4-((benzo[d][1,3]dioxol-5-yl)methyl)-dihydro-3-(hydroxy(3,4-dimethoxyphenyl) methyl) furan-2(3H)-one (PPT), with calf thymus DNA (ctDNA) has been examined using UV-Visible absorption spectrophotometry, fluorescence spectroscopy, viscosity measurement and molecular docking studies. UV-Vis absorption results showed hyperchromic effect and low binding constant value (1.01×104 M-1), indicating non-intercalative interaction as a binding mode. The competitive fluorescence study also confirmed the obtained results from UV-Vis absorption spectra. Small changes in the viscosity of DNA exhibited that the interaction of PPT with DNA is based on groove binding mode. Molecular docking study showed minor groove interaction and -7.08 kcal/mol as a calculated energy

Synthesis and In Vitro

Three 2-amino-4-(trifluoromethylphenyl)-3-cyano-7-(dimethylamino) -4H-chromene derivatives were synthesized and their cytotoxic activities were determined against six human tumor cell lines using MTT assay. Condensation of 3-(dimethylamino)phenol, trifluoromethybenzaldehydes and malonitrile in ethanol containing piperidine afforded corresponding chromenes (4a-c). The structure of the synthesized compound was confirmed by 1H NMR, IR and Mass spectral data. Among compounds tested, 3-trifluoromethyl analogue (3b) was the most active against all human tumor cell lines (IC50=12-45 nM)