Anticancer and Antiviral Sulfonamides

Abstract

The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anti- carbonic anhydrase, diuretic, hypoglycemic and antithyroid activity among others. A large number of structurally novel sulfonamide derivatives have ultimately been reported to show substantial antitumor activity in vitro and in vivo. Although they have a common chemical motif of aromatic/heterocyclic or amino acid sulfonamide, there are a variety of mechanisms of their antitumor action, such as carbonic anhydrase inhibition, cell cycle perturbation in the G1 phase, disruption of microtubule assembly, functional suppression of the transcriptional activator NF-Y, and angiogenesis (matrix metalloproteinase, MMP) inhibition among others. Some of these compounds selected via elaborate preclinical screenings or obtained through computer-based drug design, are currently being evaluated in clinical trials. The review summarizes recent classes of sulfonamides and related sulfonyl derivatives disclosed as effective tumor cell growth inhibitors, or for the treatment of different types of cancer. Another research line that progressed much in the last time regards different sulfonamides with remarkable antiviral activity. Thus, at least two clinically used HIV protease inhibitors possess sulfonamide moieties in their molecules, whereas a very large number of other derivatives are constantly being synthesized and evaluated in order to obtain compounds with less toxicity or activity against drug-resistant viruses. Several non nucleoside HIV reverse transcriptase or HIV integrase inhibitors containing sulfonamido groups were also reported. Another approach to inhibit the growth of retroviruses, including HIV, targets the ejection of zinc ions from critical zinc finger viral proteins, which has as a consequence the inhibition of viral replication in the absence of mutations leading to drug resistance phenotypes. Most compounds with antiviral activity possessing this mechanism of action incorporate in their molecules primary sulfonamide groups. Some small molecule chemokine antagonists acting as HIV entry inhibitors also possess sulfonamide functionalities in their scaffold.

Profiling the NIH Small Molecule Repository for Compounds That Generate H2O2by Redox Cycling in Reducing Environments

“…[30][31][32] The TPR2A domain of HOP contains 2 Cys sulfonamide functionality is widely used by medicinal chemists in the design of biologically active small molecules, and is often incorporated into drug candidates to improve physicochemical properties such as water solubility and bioavailability. [40][41][42] In 11 of the 15 arylsulonamide RCCs, the oxonaphthalen-1(4H)-ylidene-benzenesulfonamides and the hydroxynaphthalen-1-ylbenzenesulfonamides, the amino groups of the arylsulfonamide groups are attached at the para-position of quinone-like structures (Fig. 4C).…”

“…6 The sulfonamides constitute an important class of pharmacological agents possessing antitumor, antiviral, antibacterial, antifungal, antimalarial, diuretic, hypoglycemic, and antithyroid activity among others. [40][41][42] Sulfonamide-based inhibitors have been designed for many enzyme targets: carbonic anhydrases, aspartic proteases, serine proteases, metalloproteases, matrix metalloproteinases, steroid sulfatases, and PTPs. [40][41][42] The 6.…”

A Novel and Green Method for N-acylation of Amines and Sulfonamides under Ultrasound Irradiation

“…Sonication was performed in a FUNGILAB ultrasonic bath at a frequency of 40 kHz and nominal power 260 W. Melting points were measured in open capillary tubes on an electro thermal-apparatus. 1 H-NMR and 13 C-NMR spectra were recorded on Bruker spectrometer (400 and 100MHz) using (CDCl 3 ) as solvent and (TMS) as an internal standard. IR spectra were recorded on a PerkinElmer FT-600 spectrophotometer.…”

“…The N-acyl sulfonamide moiety is a common feature in several important bio molecules and has emerged as an important class drug synthesis [1][2][3] . A large number of novel N-acylated-sulfonamidessulfonamides molecules have been investigated for antibacterial activity 4 .…”

Synthesis and Biological Activities Evaluation of Some New 1,2,4-Triazinone Derivatives Bearing Sulfonamide Moiety

“…In addition, dorzolamide, and brinzolamide have been launched as topically acting antiglaucoma pharmacological agents [17,18]. Till date, thousands of sulfonamide derivatives, analogues, and related compounds have been synthesized, which are effective as diuretics, antimalarial, leprosy and antithyroid agents and employed for other diseases [17,19]. Moreover, aryl sulfonamides celecoxib and vadecoxib are used as COX-II inhibitors and anticancer agents [20,21].…”