Synthesis and Evaluation of Anticancer Activity of Pyrazolone Appended Triarylmethanes (TRAMs)

Abstract

The present work describes the design, synthesis, and evaluation of the anticancer properties of pyrazolone ring appended triarylmethanes by the condensation of diarylmethanols with pyrazolone in presence of a catalytic amount of p-TSA catalyst. The use of an inexpensive catalyst and accessing the desired product in good yields within a short span are the merits associated with this protocol. Furthermore, the in-silico, as well as in-vitro analysis and molecular docking of the designed molecules, were performed followed by their anticancer activity evaluation against cancer cell lines like MCF7, MDA-MB-231, HeLa, and DU-145. Few of the synthesized molecules demonstrated significant anticancer activity and could provide a new direction in the development of anti-cancer molecules.

Anticancer Agents as Design Archetypes: Insights into the Structure–Property Relationships of Ionic Liquids with a Triarylmethyl Moiety

“…Finally, we elected to employ active pharmaceutical ingredients (APIs) and their precursors to simultaneously introduce structural diversity into the ILs in a priori anticipation of reduced toxicities. The API precursors used in this endeavor include 5nitroimidazole (3), the backbone of various antimicrobial compounds, 22 methimazole (7,8), commonly used to treat hyperthyroidism, 23 and dalfampridine (9−12), a potassium channel blocker used to treat neurological disorders such as multiple sclerosis. 24 The choice to retain chloride as the anion was made to maintain low toxicity and promote other desirable ionic interactions; this limitation was deemed acceptable within the context of formulating drug-based ILs.…”

“…First reported by Lewis and Goland in 1953, the antitumor activity of organic dyes having a triarylmethyl (trityl) backbone was demonstrated by testing 235 commercially available compounds. In the period since, these triarylmethyl-bearing compounds have become well-established as anticancer agents owing, in part, to the unique structural arrangement and lipophilic nature of the trityl group. − A canonical example of this class of compounds is Clotrimazole, which was originally developed as an antifungal agent for treating fungal skin infections such as athlete’s foot and ring worm. Recently, Clotrimazole has also been shown to exhibit considerable inhibitory effects on both cancer cell proliferation and tumor growth (Figure ).…”

“…8 As such, many other triarylmethyl-containing compounds, including S-trityl-L-cysteine as well as various triphenylmethylamides and triphenylmethylphosphonates, also exhibit anticancer properties through mechanisms, which arrest cancerous cell growth at various cell cycle phases or by inducing apoptosis. 7 The primary limitation of Clotrimazole and its analogues toward cancer therapeutics stems from the incredibly poor bioavailability arising from the lipophilic nature of the triarylmethyl moiety. 9 Beyond anticancer and antifungal pharmaceuticals, triarylmethyl-based compounds have found further applications for synthetic dyes, 10−12 catalysis, 13,14 and coordination chemistry, conferring a broad relevance of the triarylmethyl group to several disciplines.…”

4-Disubstituted Pyrazolin-3-Ones—Novel Class of Fungicides against Phytopathogenic Fungi

“…The history of the medical use of 4-unsubstituted pyrazolinones began as early as 1887 with the discovery of antipyrine (1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one), one of the first nonopioid analgesics and antipyretics. This discovery prompted the study of pyrazolone derivatives, including C4-monosubstituted pyrazolones, pyrazolone-based Schiff bases, and their metal complexes, which possess anti-inflammatory, antipyretic and analgesic [22,[25][26][27], antitumor/cytotoxic [22,25,[28][29][30], antimicrobial [22,25,[31][32][33], antioxidant [22,26], and protein denaturation inhibiting [27] activities. The interest of medicinal chemists to pyrazolones has been maintained and is increasing at the present time [22].…”

Greener Synthesis, In-Silico and Theoretical Analysis of Hydrazides as Potential Antituberculosis Agents (Part 1)

“…Considering the stronger antimicrobial potentials of Hydrazide-hydrazones having the azomethine group (-NH-N=CH-), we decided to synthesize newer hydrazides using a greener catalyst, Chitosan hydrochloride, and theoretically tested (3a-3j) for their antimicrobial potentials using several computational approaches [5]. These attempts would also enlighten us on the probable anti-TB mechanisms of previously (in vitro) tested hydrazides [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] (Figure 1). Moreover, recently, our group has also reported anti-TB potentials of a variety of potent Hydrazide-hydrazone derivatives.…”