About Histone deacetylase

It's honor to me to contact you Prof. Giovina Ruberti. My name is Ahmed Mohsen Kamal, I'm a demonstrator at medicinal chemistry department-faculty of pharmacy-Assiut university-Egypt I'm working on synthesis new norfloxacin derivatives with possible antibacterial, antimycobacterial and anticancer activity. My new compounds were exposed to in-silico studies through molecular modelling and showed promising activity on histone deacetylase enzyme more than norfloxacin and SAHA. I wonder if there's any possibility to cooperate with you prof and make screening for my new compounds to determine their anticancer activity and their inhibitory effect on histone deacetylase enzyme. I have attached an excel spreadsheet with the results so far. We have all MICs against E. coli. There are several compounds with quite a good MIC, two with an MIC comparable to Nor, and one with an even better MIC. We have tested all compounds against P. aeruginosa. Less of them are active, but we have at least three with an MIC ≤ 1, which we will test again together with Nor and Cip. We have done mode of action confirmation for gyrase in E. coli, where we selected the best compounds of each series, 19 in total. 18 of those show a phenotype consistent with gyrase inhibition. We have tested off-target activity on the inner membrane of E. coli and none of the 19 tested compounds showed any effects. Next week, we plan to test outer membrane activity in E. coli with the best representative of each series. M. tuberculosis is still growing slowly. We will wait until the cultures are ready to complete the MIC assays (and we do not have 96-well plates at the moment because Covid testing has depleted the supply in Sweden, so we have to wait for that, too). Once Mtb is in log phase and we have the plates, we will test MICs against Mtb, test lower concentrations of the three best compounds against P. aeruginosa, and test S. aureus as well. After that, we will test the best compounds against quinolone-resistant P. aeruginosa and S. aureus. Then we will test effects on peptidoglycan synthesis in Gram-positives with the compounds that are most active against S. aureus. So that is the plan. Unfortunately, I cannot tell you exactly when Mtb will be ready and when we will have plates again, but I made an estimate in the excel file. I will send you updated versions of the spreadsheet when results come in.