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Fulltext Crystal structure of 3-(adamantan-1-yl)-4-(4-chloro-phen-yl)-1H-1,2,4-triazole-5(4H)-thione

Al-Wabli RI, El-Emam AA, Alroqi OS, Chidan Kumar CS, Fun HK

Acta Crystallogr E Crystallogr Commun, 2015 Feb 1;71(Pt 2):o115-6.
PMID: 25878859 DOI: 10.1107/S2056989015000596

The title compound, C18H20ClN3S, is a functionalized triazoline-3-thione derivative. The benzene ring is almost perpendic-ular to the planar 1,2,4-triazole ring [maximum deviation = 0.007 (1) Å] with a dihedral angle of 89.61 (5)° between them and there is an adamantane substituent at the 3-position of the triazole-thione ring. In the crystal, N-H⋯S hydrogen-bonding inter-actions link the mol-ecules into chains extending along the c-axis direction. The crystal packing is further stabilized by weak C-H⋯π inter-actions that link adjacent chains into a two-dimensional structure in the bc plane. The crystal studied was an inversion twin with a 0.50 (3):0.50 (3) domain ratio.

Matched MeSH terms: Adamantane
Fulltext Liver Function Test Abnormalities in Experimental and Clinical Plasmodium vivax Infection

Odedra A, Webb L, Marquart L, Britton LJ, Chalon S, Moehrle JJ, et al.

Am J Trop Med Hyg, 2020 11;103(5):1910-1917.
PMID: 32815508 DOI: 10.4269/ajtmh.20-0491

Liver transaminase elevations after treatment in malaria volunteer infection studies (VISs) have raised safety concerns. We investigated transaminase elevations from two human Plasmodium vivax VISs where subjects were treated with chloroquine (n = 24) or artefenomel (n = 8) and compared them with studies in Thailand (n = 41) and Malaysia (n = 76). In the VISs, alanine transaminase (ALT) increased to ≥ 2.5 × upper limit of normal (ULN) in 11/32 (34%) volunteers, peaking 5-8 days post-treatment. Transaminase elevations were asymptomatic, were not associated with elevated bilirubin, and resolved by day 42. The risk of an ALT ≥ 2.5 × ULN increased more than 4-fold (odds ratio [OR] 4.28; 95% CI: 1.26-14.59; P = 0.02) for every log10 increase in the parasite clearance burden (PCB), defined as the log-fold reduction in parasitemia 24 hours post-treatment. Although an elevated ALT ≥ 2.5 × ULN was more common after artefenomel than after chloroquine (5/8 [63%] versus 6/24 [25%]; OR 5.0; 95% CI: 0.91-27.47; P = 0.06), this risk disappeared when corrected for PCB. Peak ALT also correlated with peak C-reactive protein (R = 0.44; P = 0.012). Elevations in ALT (≥ 2.5 × ULN) were less common in malaria-endemic settings, occurring in 1/41 (2.5%) Thai patients treated with artefenomel, and in none of 76 Malaysians treated with chloroquine or artemisinin combination therapy. Post-treatment transaminase elevations are common in experimental P. vivax infection but do not appear to impact on participant safety. Although the mechanism of these changes remains uncertain, host inflammatory response to parasite clearance may be contributory.

Matched MeSH terms: Adamantane/analogs & derivatives*; Adamantane/therapeutic use
Effects of a neurotensin analogue (PD149163) and antagonist (SR142948A) on the scopolamine-induced deficits in a novel object discrimination task

Azmi N, Norman C, Spicer CH, Bennett GW

Behav Pharmacol, 2006 Jun;17(4):357-62.
PMID: 16914954

Various lines of evidence suggest a role in cognition for the endogenous neuropeptide, neurotensin, involving an interaction with the central nervous system cholinergic pathways. A preliminary study has shown that central administration of neurotensin enhances spatial and nonspatial working memory in the presence of scopolamine, a muscarinic receptor antagonist which induces memory deficits. Utilizing similar methods, the present study employed a two-trial novel object discrimination task to determine the acute effect of a neurotensin peptide analogue with improved metabolic stability, PD149163, on recognition memory in Lister hooded rats. Consistent with previous findings with neurotensin, animals receiving an intracerebroventricular injection of PD149163 (3 microg) significantly discriminated the novel from familiar object during the choice trial. In addition, a similar dose of PD149163 restored the scopolamine-induced deficit in novelty recognition. The restoration effect on scopolamine-induced amnesia produced by PD149163 was blocked by SR142948A, a nonselective neurotensin receptor antagonist, at a dose of 1 mg/kg (intraperitonial) but not at 0.1 mg/kg. In conclusion, the present results confirm a role for neurotensin in mediating memory processes, possibly via central cholinergic mechanisms.

Matched MeSH terms: Adamantane/analogs & derivatives; Adamantane/pharmacology
Exploring antidiabetic potential of adamantyl-thiosemicarbazones via aldose reductase (ALR2) inhibition

Shehzad MT, Hameed A, Al-Rashida M, Imran A, Uroos M, Asari A, et al.

Bioorg Chem, 2019 11;92:103244.
PMID: 31541804 DOI: 10.1016/j.bioorg.2019.103244

The role of aldose reductase (ALR2) in diabetes mellitus is well-established. Our interest in finding ALR2 inhibitors led us to explore the inhibitory potential of new thiosemicarbazones. In this study, we have synthesized adamantyl-thiosemicarbazones and screened them as aldehyde reductase (ALR1) and aldose reductase (ALR2) inhibitors. The compounds bearing phenyl 3a, 2-methylphenyl 3g and 2,6-dimethylphenyl 3m have been identified as most potent ALR2 inhibitors with IC50 values of 3.99 ± 0.38, 3.55 ± 0.26 and 1.37 ± 0.92 µM, respectively, compared with sorbinil (IC50 = 3.14 ± 0.02 μM). The compounds 3a, 3g, and 3m also inhibit ALR1 with IC50 value of 7.75 ± 0.28, 7.26 ± 0.39 and 7.04 ± 2.23 µM, respectively. Molecular docking was also performed for putative binding of potent inhibitors with target enzyme ALR2. The most potent 2,6-dimethylphenyl bearing thiosemicarbazone 3m (IC50 = 1.37 ± 0.92 µM for ALR2) and other two compound 3a and 3g could potentially lead for the development of new therapeutic agents.

Matched MeSH terms: Adamantane/chemistry*
Fulltext Dipeptidyl Peptidase-4 inhibitors use in type II diabetic patients in a tertiary hospital

Mak WY, Nagarajah JR, Abdul Halim H, Ramadas A, Mohd Pauzi Z, Pee LT, et al.

J Pharm Policy Pract, 2020;13:34.
PMID: 32566235 DOI: 10.1186/s40545-020-00238-y

Background: In Malaysia, for more than a decade, dipeptidyl peptidase-4 inhibitors (DPP-4i) are among the oral antidiabetic medications used as monotherapy or in combination to manage type II diabetes mellitus (T2DM). These medications are known for the efficacy in glycated haemoglobin (HbA1c) reduction and weight neutral effect with minimal hypoglycaemia occurrence. This study aimed to identify the outcomes of DPP-4i use in one of the largest tertiary public hospital in Southeast Asia.
Methods: This is a retrospective cross sectional study conducted in 2016, where stratified sampling method was used. Patients with T2DM treated with available DPP-4i; namely Linagliptin, Saxagliptin, Sitagliptin and Vildagliptin, for at least 3 months were identified from the pharmacy record. Medical records from Physician Clinic in Hospital Kuala Lumpur (HKL) were reviewed. Data on demographic, anthropometric, antidiabetic treatment modalities, laboratory and documented outcomes were collected. Outcomes endpoints which include changes in HbA1c, fasting blood glucose (FBG), and body weight were recorded and analysed. Adverse drug reactions (ADR) documented were also reported.
Results and discussion: A total of one hundred and five patients were recruited. The patients were 49.5% men (n = 52), with a mean age of 57 years, mean HbA1c of 8.5% (69 mmol/mol) and mean BMI of 29.5 kg/m2. At least 50% of the patients had T2DM for more than 10 years and more than two third of these patients had both T2DM and hypertension. Thirty nine patients were on Vildagliptin, 32 on Sitagliptin, 26 on Saxagliptin and the remaining on Linagliptin. The most commonly prescribed DPP-4i were Vildagliptin and Sitagliptin. Majority of the patients (90.4%) were prescribed with Metformin, with 62.8% of patients on fixed-dose combination, and the remaining on add-on Metformin therapy. Use of DPP-4i as an adjunct was associated with a mean reduction of 0.9% (9 mmol/mol) in HbA1c (p

Matched MeSH terms: Adamantane