1,2,3,4-Tetrahydroisoquinoline (THIQ) is one of the 'privileged scaffolds', commonly found in nature. Initially, this class of compounds was known for its neurotoxicity. Later on, 1-methyl-1,2,3,4-tetrahydroisoquinoline was proved as an endogeneous Parkinsonism-preventing agent in mammals. The fused THIQs have been studied for their role as anticancer antibiotics. The US FDA approval of the trabectedin for the treatment of soft tissue sarcomas, is a milestone in the anticancer drug discovery. Areas covered: This review covers the patents on various therapeutic activities of the THIQ derivatives in the years between 2010 and 2015. Patents were collected using a thorough search of Espacenet and WIPO databases. The therapeutic areas covered include cancer, malaria, central nervous system (CNS), cardiovascular, metabolic disorders, and so on. This also includes several patents on specific THIQs of clinical importance. Expert opinion: A large number of the THIQ derivatives have been synthesised for various therapeutic activities, with noticeable success in the area of drug discovery for cancer and CNS. They may also prove to be promising candidates for various infectious diseases, such as malaria, tuberculosis, HIV-infection, HSV-infection, leishmaniasis, etc. They can also be developed as novel class of drugs for various therapeutic activities with unique mechanism of action.

where a voucher specimen (No. MP-2: 28/7/2007) was kept for future reference. The seeds were dried at room temperature and mechanically powdered to obtain a coarse powder; defatted with petroleum ether (60-80°C) and Soxhlet extracted with methanol. Solvent removal under reduced pressure was afforded by methanolic extract (yield 9.5% w/w). The dry methanolic extract was stored in cool and dry place which was further used for evaluation of the hepatoprotective activity. Phytochemical ScreeningA preliminary phytochemical screening of methanolic extract of A. subulatum seeds was carried out. [4] Animals Studies were carried out using either sex Wistar albino rats (200-220 g). They were obtained from the animal house, Anand pharmacy college (APC), Anand, India. The animals were grouped and housed in polyacrylic cages (38 × 23 × 10 cm) with not more than six animals per cage and maintained under standard laboratory conditions; temperature (22 ± 2°C), relative humidity (55 ± 5 %) with dark and light cycle (12/12 hours). They were allowed free access of standard pellet diet (Amrut feed, Sangli, India) and water ad libitum. The rats were acclimatized to laboratory condition for 10 days before the commencement of experiment. Animal studies were approved by the Institutional Animal EthicsThe hepatoprotective activity of methanolic extract of Amomum subulatum Roxb (Zingiberaceae) seeds was studied against 20 % ethanol (3.76 g/kg/days, p.o for 18 days) induced liver damage in rats. Ethanol produced significant changes in various liver parameters such as functional (thiopentone-induced sleeping time) and physical (increased liver weight and volume). It also increased the biochemical parameters such as serum glutamate oxaloacetic transaminase and glutamate pyruvic transaminase, alkaline phosphatase, total and direct bilirubin, total cholesterol, triglyceride and decreased total protein along with changes in histological parameters (damage to hepatocytes). Treatment with methanolic extract of A. subulatum (100 and 300 mg/kg/day, p.o. for 18 days) and silymarin significantly prevented the functional, physical, biochemical and histological changes induced by ethanol, indicating the recovery of hepatic cells. These results demonstrate that methanolic extract of A. subulatum seeds possessed the hepatoprotective activity.

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A high-performance thin-layer chromatographic method for simultaneous determination of nadifloxacin, mometasone furoate, and miconazole nitrate was developed and validated as per International Conference on Harmonization guidelines. High-performance thin-layer chromatographic separation was performed on aluminum plates precoated with silica gel 60F and methanol:ethyl acetate:toluene: acetonitrile:3M ammonium formate in water (1:2.5:6.0:0.3:0.2, % v/v) as optimized mobile phase at detection wavelength of 224 nm. The retardation factor (R) values for nadifloxacin, mometasone furoate, and miconazole nitrate were 0.23, 0.70, and 0.59, respectively. Percent recoveries in terms of accuracy for the marketed formulation were found to be 98.35-99.76%, 99.36-99.65%, and 99.16-100.25% for nadifloxacin, mometasone furoate, and miconazole nitrate, respectively. The pooled percent relative standard deviation for repeatability and intermediate precision studies was found to be < 2% for three target analytes. The effect of four independent variables, methanol content in total mobile phase, wavelength, chamber saturation time, and solvent front, was evaluated by fractional factorial design for robustness testing. Amongst all four factors, volume of methanol in mobile phase appeared to have a possibly significant effect on retention factor of miconazole nitrate compared with the other two drugs nadifloxacin and mometasone furoate, and therefore it was important to be carefully controlled. In summary, a novel, simple, accurate, reproducible, and robust high-performance thin-layer chromatographic method was developed, which would be of use in quality control of these cream formulations.

8‐Hydroxyquinoline, being one of the privileged scaffolds, is known to possess a wide range of biological activities. 8‐Hydroxyquinoline quinoline has been explored synthetically through functionalization at different positions by different groups in search of medicinally important molecules. Herein, we synthesized twenty‐one (20 a‐20 u) different hydrazones of 8‐hydroxyquinoline at C‐2 position in good yields and characterised by 1H NMR, 13C NMR, HRMS and IR. All the synthesized compounds were evaluated for their anti‐HIV‐1 and anti‐cancer potential through in vitro cell‐based assays. Compound 20 u ((E)‐2‐((2‐(4‐methoxyphenyl)hydrazono)methyl)quinolin‐8‐ol) was found to be the most active against HIV (IC50: 1.88 and 6.27 μM; TI 73.82 and 22.07, against HIV‐1VB59 and HIV‐1UG070 respectively). Compound 20 l ((E)‐2‐((2‐(4‐fluorophenyl)hydrazono)methyl)quinolin‐8‐ol) was identified as the most cytotoxic against four cancer cell lines (IC50: 26.30, 34.19, 38.77 and 34.23 μM against HeLa, MCF‐7, A‐549 and MDA‐MB‐231, respectively) with 2.4, 1.9, 1.6, 1.9‐folds selectivity, respectively over normal cells (IC50 63.75 μM against HEK‐293 normal cells).

A accurate, precise and robust isocratic HPLC method has been developed and validated for simultaneous determination of Rifampicin and Ofloxacin. The chromatographic separation was carried out on Kinetex C 18 , 100 A Phenomenex column with a mixture of 0.03M Potassium dihydrogen phosphate buffer pH 3.0: Acetonitrile (55:45) as mobile phase at 230 nm. The retention times were 2.91 and 4.87 min for Ofloxacin and Rifampicin, respectively. Calibration plots were linear over the concentration range 1-5 and 2-10 µg/ml for Rifampicin and Ofloxacin, respectively. The method was validated for linearity, sensitivity accuracy, precision, and robustness. Percent recoveries were found to be close to 100% with low variability. Fractional factorial design with four factors was chosen for robustness testing. The volume of acetonitrile and flow rate showed significant effect on retention factor of both the drugs and asymmetry factor of ofloxacin. The method may be adopted for routine analysis at industry.

A rapid and sensitive reversed-phase high-performance liquid chromatography (HPLC) method using novel salting-out assisted liquid-liquid extraction technique has been developed for the quantitative determination of febuxostat (FEB), used for the treatment of gout, in rat plasma. The method was validated according to US FDA guideline. Separation was achieved using a Phenomenex Luna-C (250 × 4.60 mm, 5 µm) column and mobile phase composed of potassium dihydrogen orthophosphate buffer 25 mM, adjusted to pH 6.8 with triethylamine:methanol in a ratio of 35:65 (v/v) showing retention time 5.56 and 8.86 min for FEB and internal standard, respectively. The optimal salting-out parameters; 1 mL of acetonitrile and 200 µL of 2 M ammonium acetate salt showed extraction recovery >90% for FEB from plasma. This extraction procedure afforded clear samples resulting in convenient and cost-saving procedure and showed good linear relationship (r > 0.9997) between peak area ratio and concentration from 0.3 to 20 µg/mL. The results of pharmacokinetic study showed that absorption profile of spherical agglomerate of FEB compared to marketed formulation was higher indicating greater systemic absorption. In conclusion, the developed SALLE-HPLC method with simple ultraviolet detection offered a number of advantages including good quantitative ability, wide linear range, high recovery, short analysis time as well as low cost.

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