Mohammed Iqbal Choudhary

In vitro cytotoxic activity of isolated acridones alkaloids from Zanthoxylum leprieurii Guill. et Perr

Chemical investigation of the roots and fruits of Zanthoxylumleprieurii Guill. et Perr. led to the isolation of three new alkaloids including two acridone derivatives, 3-hydroxy-1,4-dimethoxy-10-methyl-9-acridone (2) and 3-hydroxy-1,2-dimethoxy-10-methyl-9-acridone (3) named helebelicine A and B, respectively, and one secobenzo[c]phenantridine, 10-O-demethyl-12-O-methylarnottianamide (10), together with thirteen other compounds. The structures of compounds 2, 3 and 10 as well as those of the known compounds were elucidated by using spectroscopic methods and by comparison with reported data. The brine-shrimp (artemia salina) lethality bioassay of the chloroform extract of the fruits showed modest cytotoxicity with LD(50) at 13.1microg/mL. Isolated compounds 1, 4-6 were found to be moderately active against lung carcinoma cells (A549), colorectal adenocarcinoma cells (DLD-1) and normal cells (WS1) with IC(50) values ranging from 27 to 77microM. In contrast to the positive control etoposide used, the cytotoxicity of the most active compound 4 was found to be selective against cancer cells in comparison to normal cells WS1 with IC(50) of 51+/-8microM and 4.3+/-0.4microM, respectively.

6-Nitrobenzimidazole derivatives: Potential phosphodiesterase inhibitors: Synthesis and structure-activity relationship

6-Nitrobenzimidazole derivatives (1-30) synthesized and their phosphodiesterase inhibitory activities determined. Out of thirty tested compounds, ten showed a varying degrees of phosphodiesterase inhibition with IC(50) values between 1.5±0.043 and 294.0±16.7 μM. Compounds 30 (IC(50)=1.5±0.043 μM), 1 (IC(50)=2.4±0.049 μM), 11 (IC(50)=5.7±0.113 μM), 13 (IC(50)=6.4±0.148 μM), 14 (IC(50)=10.5±0.51 μM), 9 (IC(50)=11.49±0.08 μM), 3 (IC(50)=63.1±1.48 μM), 10 (IC(50)=120.0±4.47 μM), and 6 (IC(50)=153.2±5.6 μM) showed excellent phosphodiesterase inhibitory activity, much superior to the standard EDTA (IC(50)=274±0.007 μM), and thus are potential molecules for the development of a new class of phosphodiesterase inhibitors. A structure-activity relationship is evaluated. All compounds are characterized by spectroscopic parameters.

Hypoglycemic activity of Buchholzia coriacea (Capparaceae) seeds in streptozotocin-induced diabetic rats and mice.

The present study evaluates the possible hypoglycemic activity and ameliorative effects of oral administration of ethanol extracts (EEBC) and butanol fraction (BFBC) of Buchholzia coriacea seeds, a plant in use traditionally for treating diabetes, hypertension, rheumatism, cold, cough and catarrh, in streptozotocin (STZ)-induced diabetic mice and rats. Fasting blood glucose (FBG) levels were evaluated before and after extracts administration. EEBC and BFBC significantly decreased (P<0.05) FBG in hyperglycemic mice and normoglycemic rats within 4 and 12 h, respectively after extract administration. The administration of EEBC, BFBC and glibenclamide (a standard antidiabetic drug) for 10 days significantly lowered (P<0.05) FBG level in STZ-induced diabetic rats by 55%, 64% and 56%, respectively. EEBC and BFBC significantly (P<0.05) decreased hepatic injury induced by STZ as evident in the decreased activity of serum alanine amino transferase and aspartate amino transferase compared to in the STZ-only treated group. Similarly, both extracts significantly decreased (P<0.05) the elevated levels of serum creatinine, urea, total cholesterol, triglyceride and thiobarbituric acid reactive species (TBARS) products in diabetic rats. Serum superoxide dismutase activity was significantly enhanced (P<0.05) by treatments with EEBC, BFBC and glibenclamide. Overall, the results suggest that B. coriacea seeds contain a potent hypoglycemic and antioxidant agent suggested to be a flavone glycoside concentrated in BFBC which may find clinical application in amelioration of diabetes-induced secondary complications.

Isoflavone Dimers and Other Bioactive Constituents from the Figs of Ficus mucuso

Phytochemical investigation of the figs of Ficus mucuso led to the isolation of three new isoflavone dimer derivatives, mucusisoflavones A-C (1-3), together with 16 known compounds. Some of the isolates were tested in vitro for their inhibitory properties toward β-glucuronidase and Plasmodium falciparum enoyl-ACP reductase (PfENR) enzymes. Compound 1 (IC₅₀) 0.68 μM) showed inhibitory activity on β-glucuronidase enzyme, while 3 (IC₅₀) 7.69 μM) exhibited a weak inhibitory activity against P. falciparum enoyl-ACP reductase (PfENR).

Cytotoxic C-Methylated Chalcones from Syzygium samarangense.

Abstract The flavonoids 2′-hydroxy-4′,6′-dimethoxy-3′-methylchalcone (1), 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (2), 2′,4′-dihydroxy-6′-methoxy-3′-methylchalcone (3), 2′,4′-dihydroxy-6′-methoxy-3′-methyldihydrochalcone (4) and 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethyldihydrochalcone (5), isolated from Syzygium samarangense. (Blume) Merr. & L.M. Perry (Myrtaceae), were subjected to cytotoxicity testing using the dimethylthiazoldiphenyl tetrazolium (MTT) assay. The cell lines used were the Chinese hamster ovarian (CHO-AA8) and the human mammary adenocarcinoma, (MCF-7 and SKBR-3). Among the test compounds, 2 exhibited significant differential cytotoxicity against the MCF-7 cell line with an IC50 of 0.0015 ± 0.0001 nM. It was also cytotoxic against the SKBR-3 cell line with an IC50 of 0.0128 ± 0.0006 nM. Doxorubicin, the positive control, had an IC50 of 2.60 ± 0.28 × 10−4 nM against the MCF-7 cell line and an IC50 of 2.76 ± 0.52 × 10−5 nM against the SKBR-3 cell line. When tested in a mechanism-based yeast bioassay for detecting DNA-damaging agents using genetically engineered Saccharomyces cerevisiae. RS322Y (RAD52) mutant strain and (LF15/11) (RAD+) wild-type strain, 2 showed significant selective cytotoxicity against the RAD52 yeast mutant strain. It had an IC12 of 0.1482 nM, as compared with the positive control, streptonigrin, which had an IC12 of 0.0134 nM. Hence, 2 is a cytotoxic natural product with potential anticancer application.

Anti-inflammatory and antinociceptive activities of Homalium letestui

Abstract Context. Homalium letestui Pellegr (Flacourtiaceae) is used in various decoctions traditionally by the Ibibios of the Niger Delta of Nigeria to treat stomach ulcer, malaria and other inflammatory diseases, as well as an aphrodisiac. Objective: To investigate the anti-inflammatory and antinociceptive activities of the stem extract of the plant. Materials and methods: The ethanol stem extract (500, 750, 1000 mg/kg, i.p.) of H. letestui was investigated for anti-inflammatory activity using carrageenan, egg albumin-induced and xylene-induced ear edema models and analgesic activity using acetic acid-induced writhing, formalin-induced paw licking and thermal-induced pain models. The ethanol extract was administered to the animals orally, 30 min to 1 h depending on the model, before induction of inflammation/pain. The LD50 was also determined. GC–MS analysis of dichloromethane fraction was carried out. Results: The extract caused a significant (p < 0.05–0.001) reduction of inflammation induced by carrageenan (8.3–70.0%), egg albumin (10.0–71.42%) and xylene (39.39–84.84%). The extract also reduced significantly (p < 0.05–0.001) pain induced by acetic acid (44.22–73.65%), formalin (55.89–79.21%) and hot plate (93.0–214.5%). The LD50 was determined to be 4.38 ± 35.72 g/kg. Discussion and conclusion: The results of this study suggest that the ethanol stem extract of H. letestui possesses anti-inflammatory and analgesic properties which may in part be mediated through the chemical constituents of the plant as revealed by the GC–MS.