Regioselective Reactions, Spectroscopic Characterization, and Cytotoxic Evaluation of Spiro‐pyrrolidine Thiophene

Abstract

Spiro‐oxo‐indole/pyrrolidine‐thiophene base possessed significant pharmacological activity. The [3 + 2] cycloaddition reactions of thia‐methine ylide respected through multi‐component reaction affording regioselective and stereoselective spiroindoline‐3,2′‐tetrahydrothiophene derivative 3. Reaction of such compound with different electrophilic and nucleophilic reagents afforded bioactive heterocyclic compounds 4–16. Biological evaluation showed that these synthesized spiro‐pyrrolidine exhibited moderate to good cytotoxic activity. Among them, compounds 7 and 14 displayed the best cytotoxic activity against MCF‐7 and Wl‐38 cells with the IC50 values of 7.02 ± 0.6 and 8.97 ± 0.9 μm (very strong), respectively. Compounds 4, 5, and 12 exhibited strong cytotoxicity's with IC50 16.28 ± 1.7, 11.16 ± 1.1, and 19.14 ± 1.7 μm, respectively, against MCF‐7 mammary gland cell line. All compound structures were supported by spectroscopic data and elemental analysis.

A Facile One‐pot Synthesis and Anticancer Evaluation of Interesting Pyrazole and Pyrimidinthione via Heterocyclic Interconversion

“…The electronic structures of compounds 5 , 6 , and 8 revealed entirely spread over all molecular structure and confirmed these energetic structures of synthesized compounds. Frontier molecular orbitals have the highest occupied molecular orbital and the lowest unoccupied molecular orbital .…”

“…Moreover, the pyrazole derivatives 5, 9, and 14 have controlled growth of pieces of tumors through their combination with triphosphate, and extension during replication leads to lesions and disruptions on DNA strands (Scheme 7) [20][21][22][23][24][25][26][27][28][29][30][31][32]. The same mechanism occurred in the 2-pyrimidinthione derivatives 6, 11, and 15, same with compounds 5, 6, 9, 11, 15, and 16.…”

Engaging Isatins in Multicomponent Reactions (MCRs) – Easy Access to Structural Diversity

“…A 3‐MCR between N ‐methylisatin, 4‐(3,4‐dichlorophenyl)‐4‐oxo‐2‐butenoic acid and thioglycolic acid allowed the preparation of spirooxindole‐tetrahydrothiophene diastereoisomers, with the cycloaddition occurring in a regioselective manner (Scheme 20). The major product could be further transformed in a wide diversity of chemical reactions [47] …”

Design, Synthesis, and Bioactivity of Spiro Derivatives Containing a Pyridine Moiety

“…3 Unlike ordinary organic compounds, spiro compounds have special characteristics, such as a rigid structure, spiro conjugation, and spiro hyperconjugation, 4,5 offering them great potential for binding with biomolecules. 6 This binding potential can somewhat change the water solubility and lipophilicity of drug molecules, facilitating the development of optimized lead molecules into drugs and reducing resistance. 7,8 Several molecules derived from spiro compounds exhibit various types of biological activities, such as insecticidal, 9 antibacterial, 10 antifungal, 11 herbicidal, 12 and antiviral activities 13 and plant growth regulator properties 14 in pesticides as well as antioxidant, 15 antitumor, 16 anticancer, 17 and anti-inflammatory activities 18 in medicine.…”