Pyrazolopyrimidine with all its isoforms occupy a noteworthy position in medicinal chemistry owing to their proven dominance in the modulation of a vast array of biological receptors, thereby mitigating numerous pathological conditions. The development of sustainable protocols, which integrate the principles of green chemistry in the synthesis process although challenging, offers the most appropriate way to conduct the sustainable synthesis of pyrazolopyrimidines. Due to the effectiveness of this nucleus and striking similarity to purines, they have been accessed using green as well as non-green protocols. Analytical techniques like 2D NMR has been employed for the confirmation of pyrazolopyrimidines and their isomers besides the conventional single-crystal X-ray diffraction (XRD). Here, considering the rising awareness of sustainable protocols, we aimed at exploring this decade for green protocols for the synthesis of pyrazolopyrimidines and furnished products in excellent yields in this review. Protocols covered in this review include synthesis using green solvent, solvent-free conditions, green catalyst, and catalyst-free reactions. Also, synthesis of pyrazolopyrimidines assisted by microwave and ultrasound, as well as ionic liquid mediated synthesis are covered. It is estimated that this review shall throw some light upon the environmentally benign protocols to produce pyrazolopyrimidines which is itself a very important nucleus in the field of medicinal chemistry.

Bio-organometallic agents confer superior physicochemical profiles inaccessible to purely organic molecules. As current chemotherapeutic regimes are maligned by the toxicity and chemoresistance of cisplatin and carboplatin, the development of an arsenal of metallodrugs becomes indispensable. Metallocenes such as ferrociphenols, JAHA, and ferrocene-labeled estradiol exhibit potent anticancer profiles. Oral squamous cell carcinomas are shown to be an excellent model to assess the impact of ferrocene-based pyrazolopyrimidines (FPPs) as chemotherapeutic agents. We show here synthesis and preliminary mechanistic investigations of FPPs in the CAL 27 cell line. The results established that some of the FPPs like 4u display strong antiproliferative behavior selectively against cisplatin-resistant oral cancer cells with an IC 50 value of 7.49 μM. It was also found to activate tumor pyruvate kinase M2 (PKM2), a critical metabolic conduit in cancer. Furthermore, 4u induced apoptosis in cells and arrested cell growth in the S-phase of the cell cycle. In silico studies established that the molecule binds at the DASA-58 binding site of PKM2.

No abstract

No abstract