tSulfated steroids function as a storage reservoir of biologically active steroid hormones. The sulfatedsteroids themselves are biologically inactive and only become active in vivo when they are convertedinto their desulfated (unconjugated) form by the enzyme steroid sulfatase (STS). Inhibitors of STS areconsidered to be potential therapeutics for the treatment of steroid-dependent cancers such as breast,prostate and endometrial cancer. The present review summarizes steroid derivatives as inhibitors of STScovering the literature from the early years of STS inhibitor development to October of 2012. A briefdiscussion of the function, structure and mechanism of STS and its role in estrogen receptor-positive(ER+) hormone-dependent breast cancer is also presented.

Steroid sulfatase (STS) catalyzes the hydrolysis of the sulfate ester group in biologically inactive sulfated steroids to give biologically active steroids. Inhibitors of STS are considered to be potential therapeutics for treating hormone-dependent cancers such as ER+ breast cancer. A series of 4-substituted 17b-arylsulfonamides of 17b-aminoestra-1,3,5(10)-trien-3-ol were prepared and examined as STS inhibitors. The presence of a NO2 or Br at the 2-position of the A-ring resulted in a decrease in potency compared to their A-ring-unsubstituted counterparts. However the presence of a nitro group or fluorine atom at the 4-position of the A-ring resulted in an increase in potency and one of these compounds exhibited a Ki app value of 1 nM. Modeling studies provided insight into how these compounds interact with active site residues. The anti-proliferative activity of the 30-Br, 30-CF3, 4-NO2-30-Br and 4-NO2-30-CF3 derivatives were examined using the NCI 60-cell-line panel and found to have mean graph midpoint values of 1.9–3.4 lM.

Steroid sulfatase (STS) catalyzes the desulfation of biologically inactive sulfated steroids to yield biologically active desulfated steroids and is currently being examined as a target for therapeutic intervention for the treatment of breast and other steroid-dependent cancers. Here we report the synthesis of a series of 17b-arylsulfonamides of 17b-aminoestra-1,3,5(10)-trien-3-ol and their evaluation as inhibitors of STS. Some of these compounds are among the most potent reversible STS inhibitors reported to date. Introducing n-alkyl groups into the 40-position of the 17b-benzenesulfonamide derivative resulted in an increase in potency with the n-butyl derivative exhibiting the best potency with an IC50 of 26 nM. A further increase in carbon units (to n-pentyl) resulted in a decrease in potency. Branching of the 40-n-propyl group resulted in a decrease in potency while branching of the 40-n-butyl group (to a tert-butyl group) resulted in a slight increase in potency (IC50 = 18 nM). Studies with 30- and 40-substituted substituted 17b-benzenesulfonamides with small electron donating and electron withdrawing groups revealed the 30-bromo and 30-trifluoromethyl derivatives to be excellent inhibitors with IC50’s of 30 and 23 nM, respectively. The 17b-20-naphthalenesulfonamide was also an excellent inhibitor (IC50 = 20 nM) while the 17b-40-phenylbenzenesulfonamide derivative was the most potent inhibitor of all the compounds studied with an IC50 of 9 nM.

Certain new derivatives of 1,2,4-triazolo[1,5-a]pyrimidines were synthesized through the reaction of 1,2,4-triazolo[1,5-a]pyrimidine-7-ol with ethyl bromoacetate to afford the ethyl acetate ester, which upon hydrazinolysis gives the corresponding hydrazide. The hydrazide is the key intermediate which was used for the synthesis of the target compounds. The structures of the new compounds were assigned by spectral and elemental methods of analyses. The synthesized compounds were tested for their in vitro antibacterial and antifungal activities. Most of the tested compounds showed comparable results with those of ampicillin and fluconazole reference drugs.

Certain new derivatives of 1,2,4-triazolo[1,5-a]pyrimidines were synthesized through the reaction of 1,2,4-triazolo[1,5-a]pyrimidine-7-ol with ethyl bromoacetate to afford the ethyl acetate ester, which upon hydrazinolysis gives the corresponding hydrazide. The hydrazide is the key intermediate which was used for the synthesis of the target compounds. The structures of the new compounds were assigned by spectral and elemental methods of analyses. The synthesized compounds were tested for their in vitro antibacterial and antifungal activities. Most of the tested compounds showed comparable results with those of ampicillin and fluconazole reference drugs.

Certain new derivatives of 1,2,4-triazolo[1,5-a]pyrimidines were synthesized through the reaction of 1,2,4-triazolo[1,5-a]pyrimidine-7-ol with ethyl bromoacetate to afford the ethyl acetate ester, which upon hydrazinolysis gives the corresponding hydrazide. The hydrazide is the key intermediate which was used for the synthesis of the target compounds. The structures of the new compounds were assigned by spectral and elemental methods of analyses. The synthesized compounds were tested for their in vitro antibacterial and antifungal activities. Most of the tested compounds showed comparable results with those of ampicillin and fluconazole reference drugs.

The use of cellulosic polymers as efficient reducing, coating agents, and stabilizers in the formulation of silver nanoparticles (AgNPs) with antioxidant and antibacterial activity was investigated. AgNPs were synthesized using different cellulosic polymers, polyethylene glycol, and without polymers using tri-sodium citrate, for comparison. The yield, morphology, size, charge, in vitro release of silver ion, and physical stability of the resulting AgNPs were evaluated. Their antioxidant activity was measured as a scavenging percentage compared with ascorbic acid, while their antibacterial activity was evaluated against different strains of bacteria. The amount of AgNPs inside bacterial cells was quantified using an ICP-OES spectrometer, and morphological examination of the bacteria was performed after AgNPs internalization. Cellulosic polymers generated physically stable AgNPs without any aggregation, which remained physically stable for 3 months at 25.0 ± 0.5 and 4.0 ± 0.5 °C. AgNPs formulated using ethylcellulose (EC) and hydroxypropyl methylcellulose (HPMC) had significant (p ≤ 0.05; ANOVA/Tukey) antibacterial activities and lower values of MIC compared to methylcellulose (MC), PEG, and AgNPs without a polymeric stabilizer. Significantly (p ≤ 0.05; ANOVA/ Tukey) more AgNPs-EC and AgNPs-HPMC were internalized in Escherichia coli cells compared to other formulations. Thus, cellulosic polymers show promise as polymers for the formulation of AgNPs with antioxidant and antibacterial activities.

Tigecycline (TIGE) is the newest tetracycline derivative antibiotic with low toxicity, it is used for management of infectious diseases caused by Gram‐positive and Gram‐negative bacteria. Hence, an efficient, selective and sensitive method was developed for analysis of TIGE in commercial formulations, human plasma and urine. The spectrofluorimetric technique based on the reaction of secondary amine moiety in TIGE with 4‐chloro‐7‐nitrobenzofurazan (NBD‐Cl) in slightly alkaline medium producing a highly fluorescent product measured at 540 nm (λex at 470 nm) after heating for 15 min at 75°C. The proposed strategy was upgraded and approved by ICH rules and bio‐analytical validated using US‐FDA recommendations. A linear relationship between fluorescence intensity and TIGE concentration was observed over the concentration range 40–500 ng mL−1 with limit of quantification (LOQ) 21.09 ng mL−1 and limit of detection (LOD) 6.96 ng mL−1.The ultra‐affectability and high selectivity of the proposed strategy permits analysis of TIGE in dosage form, human plasma and urine samples with good recovery ranged from 97.23% to 98.72% and from 99.36% to 99.80% respectively, without any interfering from matrix components. Also, the developed strategy was used to examine the stability of TIGE in human plasma and applied for pharmacokinetic investigation of TIGE.

Tigecycline (TIGE) is the newest tetracycline derivative antibiotic with low toxicity, it is used for management of infectious diseases caused by Gram‐positive and Gram‐negative bacteria. Hence, an efficient, selective and sensitive method was developed for analysis of TIGE in commercial formulations, human plasma and urine. The spectrofluorimetric technique based on the reaction of secondary amine moiety in TIGE with 4‐chloro‐7‐nitrobenzofurazan (NBD‐Cl) in slightly alkaline medium producing a highly fluorescent product measured at 540 nm (λex at 470 nm) after heating for 15 min at 75°C. The proposed strategy was upgraded and approved by ICH rules and bio‐analytical validated using US‐FDA recommendations. A linear relationship between fluorescence intensity and TIGE concentration was observed over the concentration range 40–500 ng mL−1 with limit of quantification (LOQ) 21.09 ng mL−1 and limit of detection (LOD) 6.96 ng mL−1.The ultra‐affectability and high selectivity of the proposed strategy permits analysis of TIGE in dosage form, human plasma and urine samples with good recovery ranged from 97.23% to 98.72% and from 99.36% to 99.80% respectively, without any interfering from matrix components. Also, the developed strategy was used to examine the stability of TIGE in human plasma and applied for pharmacokinetic investigation of TIGE.

Abstract Ceftazidime pentahydrate (CEF) and Vancomycin hydrochloride (VAN) are antimicrobial drugs they are used worldwide especially in developing countries for management several diseases caused by bacterial infections especially against Pseudomonas species. From this point, ultrasensitive, simple, rapid, cost effective method was developed for assay of CEF and VAN in real human plasma. The proposed spectrofluorimetric method was achieved using fluorescamine reagent. This method based on reaction of fluorescamine reagent with primary amine moiety (aromatic and aliphatic) in CEF and VAN respectively, with calibration graph from 30 to 300 ng mL−1 and 0.5–30 ng mL−1 was plotted under optimum conditions. The investigated method was developed and bio-analytically validated using ICH and US-FDA recommendations. The proposed method was successfully used for determination of the cited drugs in real human plasma with high percentage of recovery ranged from 95.72 ± 0.95% to 97.72 ± 2.02 and pharmaceutical formulations with percentage 101.55 ± 0.55% and 101.99 ± 0.43% for CEF and VAN respectively. The study was also utilized to examine the stability of the CEF and VAN in real human plasma.