Letters in Drug Design & Discovery - Volume 5, Issue 4, 2008

Human drugs may cause negative environmental effects. In Sweden systems for classification of drug environmental risk and hazard have been used for five years. Environmental data on human drugs are often missing, or reveal unfavourable environmental properties. The pharmaceutical producers should highlight environmental precaution when designing new drugs.

Effects of carbohydrate derivatives, synthesized exploring D-Glucose as starting material were studied in rat jejunum and tested in the muscarinic neurotransmission. The compounds shifted rightward and reduced maximum effect of curves for ACh. In KCl curves, they produced relaxing effects. Based on these experiments we suggest that these compounds act as non-competitive antagonists.

A series of Schiff bases 1-20 was synthesised by the condensation of isatin with primary aromatic amines. All the synthesized compounds 1-20 were randomly screened for their in vitro anti-leishmanial potential. Compounds 2, 5, 7, 10, 13 and 16 also showed good anti-leishmanial activities having IC50 value 4.77 ± 0.1, 6.85 ± 0.21, 1.84 ± 0.2, 2.44 ± 0.03, 4.70 ± 0.04 and 8.58 ± 0.04 μg/mL, respectively. Remaining compounds wit Read More

A series of novel substituted 2-[4-(2,4-dimethoxy-benzoyl)-phenoxy]-1-[4-(3-piperidin-4-yl-propyl)-piperidin- 1-yl]-ethanone sulfonamide (9a-h) benzamides (10a-h) were synthesized in order to determine their antibacterial activities and possible structure- activity relationships to improve therapeutic efficacy. The synthesized compounds were characterized by 1H-NMR, FTIR and elemental analysis. All the synthesized comp Read More

A series of phthalimido-dihydropyrimidones (19a-l) and naphthalimido-dihydropyrimidones (23a-l) have been synthesized and some representative compounds have been evaluated for their in vitro anticancer activity. Compounds 19d, 19f and 19j are selectively active against leukemia while showing moderate activity against broad spectrum of cancer cell lines. The compounds (19a-l) and (23a-l) also have been evaluated for Read More

While tissue specific effects of selective androgen receptor modulators (SARMs) outside the brain have been reported, little is known about brain specific SARMs. Here we show that SARMs upregulate androgen receptor levels in brain following castration and antagonize impairments in hippocampus-dependent novel location recognition and spatial memory retention in apoE4 female mice. Together with the reduced and Read More

A series of 2,4- and 4,6-diaminopyrimidines were prepared and evaluated for their in vitro antimalarial activity. Of the 12 compounds tested 7 showed reasonable activity with 1 having a sub-micromolar IC50.

A Quantitative structure-activity relationship study (QSAR) has been made on a novel series of hydroxamic acid-based matrix metalloproteinase (MMP) inhibitors. The inhibition potencies of the compounds against two MMPs, MMP-2 and MMP-3, are found to be significantly correlated with Kier's first-order valence molecular connectivity index (1xv) and Hammett's electronic constant σ of the substituents. It is thus found tha Read More

Arylidene barbiturates 2-19 have been synthesized and their antioxidant and cytotoxic potentials have been evaluated. These compounds showed a moderate to excellent antioxidant activity in relevant antioxidant assay with no toxicity. A structure-activity relationship has been discussed. All the compounds were fully characterized by spectroscopic techniques.

Through the optimization of the active metabolite 2 of the piperidine derivative 1, we discovered a potent new drug candidate for the treatment of RA, Y-320 that inhibits T cell activation induced by IL-15 and shows a therapeutic effect on collagen-induced arthritis in DBA/1J mice. Design and structure-activity relationships are described.

The effects exerted by cocaine, amphetamine and phencyclidine on the acute opiate withdrawal induced by morphine were investigated in vitro. The results of our experiments indicate that cocaine, amphetamine and phencyclidine are able to influence opiate withdrawal in vitro thus confirming an important functional interaction between the dopaminergic system and opioid withdrawal.

We describe the case of a patient with refractory bipolar II depression who developed tolerance to lamotrigine and after failing to respond to dose escalation showed a robust response to a retrial of lamotrigine following a two week drug holiday.

A series of novel tetrahydroisoquinoline derivatives (7a-b and 8a-j) were synthesized by using N-cyanoguanyl as a spacer, and their multidrug resistance reversal activities against K562/A02 cell line in vitro were evaluated by MTT method. It was found that 7a and 8b showed more potent multidrug resistance reversal activities than verapamil.