Synthesis and docking studies of N-(5-(alkylthio)-1,3,4-oxadiazol-2-yl)methyl)benzamide analogues as potential alkaline phosphatase inhibitors

A series of N-(5-(alkylthio)-1,3,4-oxadiazol-2-yl)methyl)benzamides 6a–i were synthesized as alkaline phosphatase inhibitors. The intermediate 5-substituted 1,3,4-oxadiazole-2-thione 4 was synthesized starting with hippuric acid. Hippuric acid in the first step was converted into corresponding methyl ester 2 which upon reaction with hydrazine hydrate furnished the formation of hydrazide 3 . The hippuric acid hydrazide was then cyclized into 5-substituted 1,3,4-oxadiazole-2-thione 4 . The intermediate 4 was then reacted with alkyl or aryl halides 5a–5i to afford the title compounds N-(5-(methylthio)-1,3,4-oxadiazol-2-yl)methyl)benzamides 6a–i . The bioassay results showed that compounds 6a–i exhibited good to excellent alkaline phosphatase inhibitory activity. The most potent activity was exhibited by the compound 6i having IC₅₀ value 0.420 μM, whereas IC₅₀ value of standard (KH₂PO₄) was 2.80 μM. Molecular docking studies was performed against alkaline phosphatase enzyme (PDBID 1EW2) to check binding affinity of the synthesized compounds 6a–i against target protein. The docking results showed that three compounds 6c , 6e , and 6i have maximum binding interactions with binding energy values of −8 kcal/mol. The compound 6i displayed the interactions of oxadiazole ring nitrogen with amino acid His265 having a binding distance 2.13 Ǻ. It was concluded from our results that synthesized compounds, especially compound 6i may serve as lead structure to design more potent inhibitors of human alkaline phosphatase.     

A critical comparative ethnographic study of courtesy stigma in two leprosy-impacted communities in Indonesia

ABSTRACT

Leprosy stigma is more neglected than the disease itself since global interventions towards leprosy are focused on the medicalisation of individual-sufferers and statistical counting of documented cases and less prioritising the impact of leprosy stigma towards society. This paper examines the impact of courtesy stigma on society through comparative ethnographic method conducted in two sites in East Java Province, Indonesia. Investigation in the first site, Mandangin Island, found that the island suffers underdevelopment of public facilities such as clinics and clean water and migration and medical knowledge bottlenecks. In the second site, Sumberglagah village, leprosy patients and the community they live with are also socially separated from the locals and they are engaged in controversial businesses exploiting the public fear of leprosy. This study finds that leprosy stigma in two leprosy-impacted communities in East Java, Indonesia, does not only isolate individuals but also a whole community from a bigger society regardless of whether all of the community members have leprosy. This study also detects problems related to leprosy education within the two impacted communities. It is suggested that efforts to address the problems require holistic approaches and commitments from various actors in the area in complement to existing global health missions.     

The prognostic and predictive role of 21-gene recurrence scores in hormone receptor-positive early-stage breast cancer

Over the past two decades, gene expression profiling of breast cancer has emerged as an important tool in early-stage breast cancer management. The approach provides important information on underlying biological mechanisms, breast cancer classification, future risk potential of developing recurrent metastatic disease, and provides beneficial clues for adjuvant chemotherapy in hormone receptor (HR) positive breast cancer. Of the commercially available genomic tests for breast cancer, the prognostic and predictive value of 21-gene recurrence score tests have been validated using both retrospective data and prospective clinical trials. In this paper, we reviewed the current evidence on 21-gene expression profiles for HR-positive HER2-negative early-stage breast cancer management. We show that current evidence supports endocrine therapy alone as an appropriate adjuvant systemic therapy for approximately 70% of women with HR-positive, HER2-negative, node-negative breast cancer. Evolving evidence also suggests that 21-gene recurrence scores have predictive values for node-positive breast cancer and that chemotherapy can be avoided in more than half of women with nodes 1 to 3 positive HR-positive breast cancer. Furthermore, retrospective data also supports the predictive role of 21-gene recurrence scores for adjuvant radiation therapy. A prospective trial in this area is ongoing.     

A Miniaturized Antenna with Negative Index Metamaterial Based on Modified SRR and CLS Unit Cell for UWB Microwave Imaging Applications

A miniaturized antenna employing a negative index metamaterial with modified split-ring resonator (SRR) and capacitance-loaded strip (CLS) unit cells is presented for Ultra wideband (UWB) microwave imaging applications. Four left-handed (LH) metamaterial (MTM) unit cells are located along one axis of the antenna as the radiating element. Each left-handed metamaterial unit cell combines a modified split-ring resonator (SRR) with a capacitance-loaded strip (CLS) to obtain a design architecture that simultaneously exhibits both negative permittivity and negative permeability, which ensures a stable negative refractive index to improve the antenna performance for microwave imaging. The antenna structure, with dimension of 16 × 21 × 1.6 mm³, is printed on a low dielectric FR4 material with a slotted ground plane and a microstrip feed. The measured reflection coefficient demonstrates that this antenna attains 114.5% bandwidth covering the frequency band of 3.4–12.5 GHz for a voltage standing wave ratio of less than 2 with a maximum gain of 5.16 dBi at 10.15 GHz. There is a stable harmony between the simulated and measured results that indicate improved nearly omni-directional radiation characteristics within the operational frequency band. The stable surface current distribution, negative refractive index characteristic, considerable gain and radiation properties make this proposed negative index metamaterial antenna optimal for UWB microwave imaging applications.