Discovery of 4-(2-(dimethylamino)ethoxy)benzohydrazide derivatives as prospective microtubule affinity regulating kinase 4 inhibitors

Microtubule affinity regulating kinase 4 (MARK4) is a Ser/Thr kinase, considered as a potential drug target for cancer, diabetes and neurodegenerative diseases. Due to its significant role in the development and progression of cancer, different in-house libraries of synthesized small molecules were screened to identify potential MARK4 inhibitors. A small library of hydrazone compounds showed a considerable binding affinity to MARK4. The selected compounds were further scrutinized using an enzyme inhibition assay and finally two hydrazone derivatives (H4 and H19) were selected that show excellent inhibition (nM range). These compounds have a strong binding affinity for MARK4 and moderate binding with human serum albumin. Anticancer studies were performed on MCF-7 and A549 cells, suggesting H4 and H19 selectively inhibit the growth of cancer cells. The IC₅₀ value of compound H4 and H19 was found to be 27.39 μM and 34.37 μM for MCF-7 cells, while for A549 cells it was 45.24 μM and 61.50 μM, respectively. These compounds inhibited the colonogenic potential of cancer cells and induced apoptosis. Overall findings reflect that hydrazones/hydrazone derivatives could be exploited as potential lead molecules for developing effective anticancer therapies via targeting MARK4.

Inhibition studies of MARK4 with selected hydrazone derivatives.     

A rare case of unicondylar medial Hoffa fracture associated with ipsilateral vertical patella fracture

An 18 year old male patient was hit by a car to his motorcycle causing a unicondylar Hoffa fracture and an ipsilateral patella fracture. Hoffa fracture is a rare lesion and this association of injury has not been reported before.     

Correction: Pharmacophore-based approaches in the rational repurposing technique for FDA approved drugs targeting SARS-CoV-2 Mpro

Correction for ‘Pharmacophore-based approaches in the rational repurposing technique for FDA approved drugs targeting SARS-CoV-2 M^pro’ by Vishal M. Balaramnavar et al., RSC Adv., 2020, 10, 40264–40275, DOI: 10.1039/D0RA06038K.

The authors regret that the name of one of the authors (Talha Jawaid) was shown incorrectly in the original article. The corrected author list is as shown above.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Being an identity-release donor: a qualitative study exploring the motivations,experiences and future expectations of current UK egg donors

The objective of this study was to examine the motivations, experiences and future expectations of identity-release egg donors in the UK following the removal of donor anonymity and the increase in financial compensation for egg donation. This exploratory, in-depth qualitative study comprised semi-structured interviews with 11 women who had attended an egg donation screening appointment at a UK clinic during a four-month period in 2014. Interviews were conducted two to six weeks after the woman had donated or had withdrawn/been rejected from the donation process. Participants’ primary motivation for donating was to help infertile women have their ‘own child’, and the recent increase in financial compensation did not seem to play a significant role in their decision. All were happy to be identifiable and contacted by children born as a result of their donation. However, some were hesitant about providing non-identifying information about themselves for these offspring and wished for further information about the recipient(s) of their eggs and the outcome of their donation. Whilst this study was limited due to the small sample size, it is the first study of UK egg donors following the rise in donor compensation and suggests that other strategies may be more effective in increasing donor numbers.     

Evaluation of the effect of acetazolamide versus mannitol on cisplatin-induced nephrotoxicity,a pilot study

Background Cisplatin-induced nephrotoxicity still occurs despite the intensive hydration approach adapted to prevent its occurrence. Objective Evaluation of the effect of acetazolamide (ACTZ) on minimizing cisplatin-induced nephrotoxicity compared to mannitol when added to hydration regimen. Setting Nasser Institute Cancer Center (NICC), Cairo, Egypt. Method A total of 35 patients planned to receive cisplatin were divided into two groups: 20 patients received mannitol and 15 patients received ACTZ. Both groups received standard hydration measures as well for prevention of cisplatin-induced nephrotoxicity. Main outcome measure Patients’ kidney function was assessed using serum creatinine, creatinine clearance and blood urea nitrogen. Kidney injury was assessed using RIFLE criteria. Patients’ liver function tests and hematological parameters were also monitored. Results Patients in the mannitol group showed higher risk of developing kidney injury (30%) whereas those in the ACTZ group showed lower risk (8.9%), relative risk (RR) 0.269, 95% CI 0.108–0.815. No statistically significant difference occurred between the two groups concerning liver function tests or hematological parameters. Conclusion Use of ACTZ in addition to intensive hydration may have more beneficial effect on minimizing cisplatin-induced nephrotoxicity compared to mannitol plus intensive hydration approach. A large multicenter randomized clinical trials is recommended to confirm study results and to assess effect of ACTZ on tumor response.