Q2. What are the future works mentioned in the paper "Recent advances in microtubule-stabilizing agents" ?
Besides, perhaps the authors can consider that using some natural products with explicit pharmacophores, such as the side chain of Taxol, and small molecules, for example, benzimidazole, benzoxazole and benzothiazole with a hydroxyl group, to make a M AN US CR IP T AC CE PT ED 42 / 55 coupling in organic synthesis, then study their activity to get some potential anticancer compounds in the future designing of MSAs. It will be a future development direction of these compounds that to confirm the pharmacophore of MSAs with better therapeutic effects, then to simplify the complex structures or direct synthesize the compounds with similar structures and pharmacophores by natural products combined with chemical synthesis, finally to develop more novel, effective MSAs with low toxicity even without side effects. In a word, the unclear bioactivity, SAR and mechanism of action of some MSAs need to be studied in-depth in the future, so do the structure simplification and chemistry synthesis. Undoubtedly, MSAs will be more and more widely applied in future cancer treatments, even they might alter microtubule dynamics in neurodegenerative diseases, such as Alzheimer ’ s disease, and have the therapeutic potential of these modern diseases [ 195 ].
Q3. What is the main advantage of epothilones?
Based on the challenges that fermentation faced, undoubtedly, the chemical modification is going to be the mainstream in epothilones’ research due to its great advantage of fast and efficiently getting epothilones products.
Q4. What is the role of paclitaxel in the study of cervical cancer?
Paclitaxel is the first compound with the activity of stabling microtubules, creating a new field of anticancer drug research and making the study of paclitaxel a novel hotspot in natural medicine research in recent 30 years.
Q5. how many steps did they take to synthesize (-)-dactyloli?
In 2009, Uenishi et al. [124] achieved the total synthesis of (-)-dactylolide in 17 linear steps at an overall yield of 6.5% starting from commercial (R)-glycidol, and made it come true that (-)-zampanolide was derived synthetically from (-)-dactylolide in one step.
Q6. What is the role of the epothilones in the development of drug resistance?
In order to identify the molecular factors involved in the emergence of drug resistance induced by four tubulin mutations, Navarrete et al. [45] investigated the structure and dynamic properties of epothilone-β-tubulin complexes with wild-type and mutated tubulin by using molecular dynamic simulations, which is helpful to conduct in-depth understanding on the epothilones’ action mechanism and SAR.
Q7. What is the role of the epoxide moiety in laulimalide?
In 2002, Hamel et al. [142] discovered that a laulimalide analog lacking the epoxide moiety whose activity is between laulimalide and isolaulimalide in biochemical and cellular systems, which suggests that the epoxide moiety of laulimalide may be not an essential feature for the activity of this new drug family.
Q8. How did Taylor and coworkers synthesize peloruside A?
In 2012, Taylor et al. [165] synthesized a set of conformational analogs of peloruside A just in 18 steps from commercial materials by a simple esterification-based fragments coupling and a late stage RCM reaction.
Q9. What was the first time this group reported the third-generation total synthesis of (+)-?
Soon after, this group reported the third-generation total synthesis of (+)-discodermolide again, which was accomplished at an overall yield of 11.1% over 21 linear steps [110].
Q10. What is the way to control the stereo-selectivity of the products?
This strategy can not control the stereo-selectivity effectively leading the products to form β-glycosidic bond entirely, and they only obtained a 2.4% yield of an 8:1 mixture of β- and α-product under a strict condition control [119].
Q11. What is the evidence of MT abnormalities in a number of neurodegenerative diseases?
Brunden et al. made a detailed review that the evidence of MT abnormalities in a number of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and traumatic brain injury, which suggested that MT-stabilizing drugs hold promise for the potential treatment of several neurodegenerative diseases [197].