Multicomponent Reactions for Generation of Molecular Libraries in Anticancer Drug Discovery

Saquib, Mohammad; Khan, Mohammad Faheem; Ansari, Mohammad Imran; Khan, Irfan; Hussain, Mohammad Kamil; Singh, Jagdamba

doi:10.1201/9781315369754-5

Cited by 1 publication

(1 citation statement)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Multicomponent reactions (MCRs) are one-pot processes, in which at least three easily accessible or commercially available reagents are combined sequentially to form complex products, where most of the atoms come from the starting reagents [12,13]. Moreover, MCRs have been used successfully to synthesize novel drug-like anticancer compounds (including polyheterocycles) [14] with different associated and specific action mechanisms; for instance, by inhibition of (i) tubulin polymerization; (ii) kinesins; (iii) kinases; (iv) multidomain extra-terminal (MET) proteins; (v) p53 activity; (vi) transcription initiation factor (TIF) proteins; or vii) topoisomerases (TOP), just to highlight a few [15]. In this context, one of the most important biological targets in the fight against cancer are the tubulins, which belong to microtubules (specifically the α and the β) involved in mitosis processes [16,17,18].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Pyrrolo[3,4-b]pyridin-5-ones via Multicomponent Reactions and In Vitro–In Silico Studies Against SiHa, HeLa, and CaSki Human Cervical Carcinoma Cell Lines

et al. 2019

View full text Add to dashboard Cite

A series of 12 polysubstituted pyrrolo[3,4-b]pyridin-5-ones were synthesized via a one-pot cascade process (Ugi–3CR/aza Diels-Alder/N-acylation/decarboxylation/dehydration) and studied in vitro using human epithelial cervical carcinoma SiHa, HeLa, and CaSki cell line cultures. Three compounds of the series exhibited significative cytotoxicity against the three cell lines, with HeLa being the most sensitive one. Then, based on these results, in silico studies by docking techniques were performed using Paclitaxel as a reference and αβ-tubulin as the selected biological target. Worth highlighting is that strong hydrophobic interactions were observed between the three active molecules and the reference drug Paclitaxel, to the αβ-tubulin. In consequence, it was determined that hydrophobic–aromatic moieties of bioactive compounds and Paclitaxel play a key role in making stronger interactions to the ligand–target complex. A quantitative structure activity relationship (QSAR) study revealed that the six membered rings are the most significant molecular frameworks, being present in all proposed models for the in vitro-studied cell lines. Finally, also from the docking interpretation, a ligand-based pharmacophore model is proposed in order to find further potential polyheterocyclic candidates to bind stronger to the αβ-tubulin.

show abstract