Tanvir Khaliq

Peganine hydrochloride dihydrate an orally active antileishmanial agent.

Protozoic infections caused by genus Leishmania pose an enormous public health threat in developing countries, compounded by the toxicity and resistance to current therapies. Under the aegis of our ongoing program on drug discovery and development on antileishmanial agents from plants, we carried out bioassay guided fractionation on Peganum harmala seeds which resulted in the isolation of 1 as an antileishmanial agent. 2D-NMR spectral data and single crystal X-ray crystallography data indicated 1 as peganine hydrochloride in dihydrated form. The compound 1 exhibited in-vitro activity against both extracellular promastigotes as well as intracellular amastigotes residing within murine macrophages in Leishmania donovani. Furthermore, 1 also exhibited in-vivo activity, 79.6 (+/-8.07)% against established VL in hamsters at a dose of 100mg/kgb.wt.

Synthesis, structure-activity relationships, and biological studies of chromenochalcones as potential antileishmanial agents.

Antileishmanial activities of a library of synthetic chalcone analogues have been examined. Among them, five compounds (11, 14, 16, 17, 22, and 24) exhibited better activity than the marketed drug miltefosine in in vitro studies against the intracellular amastigotes form of Leishmania donovani. Three promising compounds, 16, 17, and 22, were tested in a L. donovani/hamster model. Oral administration of chalcone 16, at a concentration of 100 mg/kg of body weight per day for 5 consecutive days, resulted in >84% parasite inhibition at day 7 post-treatment and it retained the activity until day 28. The molecular and immunological studies revealed that compound 16 has a dual nature to act as a direct parasite killing agent and as a host immunostimulant. Pharmacokinetics and serum albumin binding studies also suggest that compound 16 has the potential to be a candidate for the treatment of the nonhealing form of leishmaniasis.

Antidyslipidemic Activity of Indigofera tinctoria

Indigofera tinctoria is a perennial shrub, which belongs to the family Papilionaceae. As a part of our drug discovery program we have investigated the antidyslipidemic activity of the alcoholic extract from Indigofera tinctoria as well as its three other components, that is, chloroform, butanol and aqueous fractions in dyslipidemic hamsters that were fed a high fat diet. The chloroform fraction showed a significant decrease in the plasma triglycerides (TG, 52%) (P < 0.001), total cholesterol (TC, 29%) (P < 0.05), glycerol (Gly, 24%) and free fatty acids (FFA, 14%). This decrease was also accompanied by an increase in high density lipoproteins (HDL) by 9% and an increased HDL-C/TC ratio of 52% at the dose of 250 mg/kg of body weight.

Anti-diabetic and anti-oxidative effects of 4-hydroxypipecolic acid in C57BL/KsJ-db/db mice

Hypoglycemic effect of ethanol extracts of Peganum harmala (commonly known as ‘Harmal’) seeds has been reported on normal and streptozotocin-induced diabetic rats. In the present study, the authors determine anti-diabetic and anti-oxidative properties of 4-hydroxypipecolic acid (4-HPA) isolated from seeds of P. harmala in C57BL/KsJ-db/db mice. Twelve week old male mice were administered 50 mg/kg body weight (4-HPA suspension were made in 1% gum acacia) for the period of 10 days, and a significant reduction in the fasting blood glucose, plasma triglycerides (TG), cholesterol, free fatty acid, low-density lipoprotein-cholesterol and a significant increase in high-density lipoprotein-cholesterol level was observed with respect to vehicle-treated db/db mice. The anti-oxidant activity of 4-hydroxypipecolic acid was studied in liver and kidney tissues by assessing malondialdehyde levels for lipid peroxidation and enzyme activity of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). Treatment of 4-HPA significantly lowered the lipid peroxidation in hepatic and renal tissue and increased the activity of CAT, GSH-Px and SOD in treated mice.

13C NMR spectroscopy of D and B, D-ring seco-limonoids of Meliaceae family§

The modified limonoids isolated from the Meliaceae are too complex or obtained in too small quantities to determine their structures by chemical and spectroscopic means, including 1H NMR. One method of dealing with such problem is direct crystallographic analysis, without or having a heavy atom, which requires an able crystallographic collaborator. The determination of the structure Utilin is one example. The analysis of the 13C NMR spectral data for different compounds has been very useful for the identification of the various skeletal types of limonoids and also for the determination of the substitution pattern. Owing to the great utilities that these data could help the scientific community, who are working in the area of limonoids, we here describe the application of NMR spectroscopy in the structure elucidation of D and B, D-ring seco-limonoids and a collection of 177 compounds 13C NMR spectral data. §This is CDRI manuscript No. 6675.

Anti-secretory and cyto-protective effects of peganine hydrochloride isolated from the seeds of Peganum harmala on gastric ulcers.

Gastroprotective mechanism of peganine hydrochloride isolated from Peganum harmala seeds was investigated. Peganine hydrochloride was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats. Potential anti-ulcer activity of peganine was observed against CRU (50.0%), AS (58.5%), AL (89.41%) and PL (62.50%) induced ulcer models. The reference drug omeprazole (10mg/kg, p.o.) showed 77.45% protection against CRU, 49.97% against AS and 69.42% against PL model. Sucralfate, another reference drug (500mg/kg, p.o.) showed 62.50% protection in AL induced ulcer model. Peganine significantly reduced free acidity (33.38%), total acidity (38.09%) and upregulated mucin secretion by 67.91%, respectively. Further, peagnine significantly inhibited H(+) K(+)-ATPase activity in vitro with IC50 of 73.47μg/ml as compared to the IC50 value of omeprazole (30.24μg/ml) confirming its anti-secretory activity.

Therapeutic Potential of Harmala ( Peganum harmala L.) Seeds with an Array of Pharmacological Activities

Publisher Summary This chapter provides an account of the pharmacological properties of P. harmala L. (Pgh) seeds, which are used in traditional medicine in regions where it occurs naturally. Peganum harmala seeds are antispasmodic, hypnotic, antiperiodic, emetic, alterative, anthelmintic, and narcotic. Powdered seed is recommended as an anthelmintic, and decoctions of the seeds and of the leaves are given in laryngitis and in rheumatism, respectively. Pgh seeds possess significant antitumor activity, having high cell toxicity and reducing the proliferation of tumoral cell lines in vitro. It is used as an analgesic and anti-inflammatory agent, as its alkaloids exhibit active analgesic properties that act on the central and peripheral nervous systems and that may be mediated by opioid receptors. Smoke from Pgh seeds kills algae, bacteria, intestinal parasites, and molds. Pgh has antibacterial activity against drug-resistant bacteria and protozoa. Pgh also has antioxidant and antimutagenic properties. The β-carboline alkaloids present in Pgh have recently drawn attention due to their antitumor activities. They have shown effectiveness against various tumor cell lines both in vitro and in vivo. Although harmala has traditionally been used as an abortifacient agent, there are few reports regarding its human toxic effects and syndromes. Symptoms of Pgh toxicity mainly consist of neurosensorial symptoms, hallucinations, a slight elevation of body temperature, and cardiovascular disorders such as bradycardia and low blood pressure; however, signs of intoxication disappear a few hours after ingestion.