Probing 4-(diethylamino)-salicylaldehyde-based thiosemicarbazones as multi-target directed ligands against cholinesterases, carbonic anhydrases and α-glycosidase enzymes.

With the fading of 'one drug-one target' approach, Multi-Target-Directed Ligands (MTDL) has become a central idea in modern Medicinal Chemistry. The present study aimed to design, develop and characterize a novel series of 4-(Diethylamino)-salicylaldehyde based thiosemicarbazones (3a-p) and evaluates their biological activity against cholinesterase, carbonic anhydrases and α-glycosidase enzymes. The hCA I isoform was inhibited by these novel 4-(diethylamino)-salicylaldehyde-based thiosemicarbazones (3a-p) in low nanomolar levels, the Ki of which differed between 407.73 ± 43.71 and 1104.11 ± 80.66 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 323.04 ± 56.88 to 991.62 ± 77.26 nM. Also, these novel 4-(diethylamino)-salicylaldehyde based thiosemicarbazones (3a-p) effectively inhibited AChE, with Ki values in the range of 121.74 ± 23.52 to 548.63 ± 73.74 nM. For BChE, Ki values were obtained with in the range of 132.85 ± 12.53 to 618.53 ± 74.23 nM. For α-glycosidase, the most effective Ki values of 3b, 3k, and 3g were with Ki values of 77.85 ± 10.64, 96.15 ± 9.64, and 124.95 ± 11.44 nM, respectively. We have identified inhibition mechanism of 3b, 3g, 3k, and 3n on α-glycosidase AChE, hCA I, hCA II, and BChE enzyme activities. Hydrazine-1-carbothioamide and hydroxybenzylidene moieties of compounds play an important role in the inhibition of AChE, hCA I, and hCA II enzymes. Hydroxybenzylidene moieties are critical for inhibition of both BChE and α-glycosidase enzymes. The findings of in vitro and in silico evaluations indicate 4-(diethylamino)-salicylaldehyde-based thiosemicarbazone scaffold to be a promising hit for drug development for multifactorial diseases like Alzheimer's disease.

An evidence-based systematic review of vitamin A by the natural standard research collaboration.

An evidence-based systematic review of vitamin A by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated and reproducible grading rationale. This paper includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Essiac: systematic review by the natural standard research collaboration.

The objective of this study was to evaluate the scientific evidence on the safety and efficacy of Essiac. This review serves as a clinical support tool. Electronic searches were conducted in 10 databases, 20 additional journals (not indexed in common databases), and bibliographies from 50 selected secondary references. No restrictions were placed on the language or quality of the publications. Standardized inclusion and exclusion criteria were used for selection. A review of the literature on Essiac and essiac formulations showed a lack of high-quality clinical trials to substantiate any of Essiac's traditional uses. Weak evidence from preclinical, animal, and laboratory data warranted a discussion regarding Essiac's use for cancer, but the results are inconclusive. Several other essiac preparations are noted in the literature, adding confusion to the exact formula and its proposed benefits. In general, there is a lack of both safety and efficacy data for Essiac and essiac formulations. Well-designed trials testing Essiac or individual herbal components are necessary to make firm recommendations.

An evidence-based systematic review of bilberry (Vaccinium myrtillus) by the Natural Standard Research Collaboration.

An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Fenugreek (Trigonella foenum-graecum L. Leguminosae): an evidence-based systematic review by the natural standard research collaboration.

An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology and dosing.

Evidence-based systematic review of saw palmetto by the Natural Standard Research Collaboration.

Here presented is an evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Boswellia: an evidence-based systematic review by the Natural Standard Research Collaboration.

An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Malignant tumors of the oral cavity and oropharynx: clinical, pathologic, and radiologic evaluation.

Carcinomas of the oral cavity and oropharynx constitute approximately 2% to 5% of head and neck cancers. Alcohol abuse and tobacco chewing, including chewing Shamma, predispose individuals to the development of cancer in the oral cavity. CT and MR imaging are best suited in the evaluation of cancer of the oral cavity and oropharynx. CT in the axial and coronal planes with 3- to 5-mm sections is the primary modality and is best in the evaluation of bony erosion of the mandible and maxilla. Furthermore, lymph node metastases in the neck are optimally evaluated by contrast CT with 5-mm axial sections. MR imaging is preferred for soft tissue assessment because of the greater contrast resolution. It is therefore the first modality in the assessment of tongue carcinomas, oropharyngeal cancer, and tonsillar lesions. The MR examination should be performed with thin-section imaging, applying T1, T2, and T1-GD-DTPA in the axial and coronal planes, with sagittal sections added for paramidline lesions involving the tongue, lips, anterior floor of the mouth, subdivided according to anatomic locations. The local spread, lymph node metastases, prognosis, and therapeutic approaches vary with the location of the lesion represented by a carcinoma either squamous or undifferentiated in 90% of cases. Some malignant lesions may mimic a benign tumor, such as the adenoid cystic or mucoepidermoid carcinoma. Histopathologic diagnosis is therefore necessary for the final diagnosis before treatment by surgery or radiotherapy. PET scanning is indicated in the following instances: in search of an unknown primary tumor in patients who have a neck mass secondary to carcinoma, if a recurrent carcinoma may be present, when there are metastatic N0 lymph nodes in the neck, or where CT is inconclusive for metastatic lymph nodes in the neck.

Red clover (Trifolium pratense) monograph: a clinical decision support tool.

Red clover, a legume resembling soy is used by man as a phytoestrogen. Other uses include asthma, pertussis, cancer and gout. The authors systematically review this herb in terms of pharmacology, efficacy, safety, side effects, standardization, dosing, toxicology as well as other parameters.