Daniel L. da Silva

Free radical scavenging and antiproliferative properties of Biginelli adducts.

A series of Biginelli adducts bearing different substituents at C-4 position were synthesized by using p-sulfonic acid calix[4]arene as a catalyst. The in vitro potential to scavenge reactive nitrogen/oxygen species (RNS and ROS) and the ability to inhibit cancer cells growth were then investigated. Four adducts were found to be potent scavengers of 2,2-diphenyl-1-picrylhydrazyl (RNS) and/or superoxide anion (ROS) radicals. The antiproliferative activity against cancer cells was disclosed for the first time for 16 monastrol analogs. The capacity of all compounds to inhibit cancer cells growth was dependent on the histological origin of cells, except for BA24, which was highly active against all cell lines. BA20 and BA33 were as potent as the reference drug doxorubicin against adriamycin-resistant ovarian and prostate cancer cells, respectively. These results highlight some monastrol analogs as lead compounds for the design of new free radical scavengers and anticancer agents.

A mini-review on Biginelli adducts with notable pharmacological properties

Graphical abstract

Calix[n]arenes in Action: Useful Host-Guest Catalysis in Organic Chemistry

The advent of host-guest catalysis brought about the prospect of a complementary mode of catalysis, with the potential for sav- ings in cost, time and energy, easier experimental procedures, and reductions in chemical waste. Water-soluble calix(n)arene catalytic systems provide additional options in biphasic catalysis for organic chemistry and process engineering. The use of calix(n)arene as host- guest catalysis developed in recent years has shown promising results since calix(n)arenes have been widely used as three-dimensional molecular platforms for the design of artificial molecular receptors, due to the availability of cheap starting materials and the facile modification of the calix(n)arene structure at the wide and narrow rims.

Synthesis and Anti-Paracoccidioides Activity of Calix(n)arenes

Fungi are some of the most neglected pathogens in terms of new drug discovery. Paracoccidioidomycosis, an endemic disease to South America, is caused by dimorphic fungi of Paracoccidioides genus. Reasonable citotoxicity, limited efficacy, and frequent use of current commercial antifungals have led to the emergence of resistance. Thus, the development of new antifungals with more selectivity and large spectrum of action is mandatory. In this work, six calix(n)arenes were synthesized and their activity explored against seven isolates of P. brasiliensis and P. lutzii. p-tert- Butylcalix(4)arene (CX1) was the most potent compound against fungal cells and exhibited the lowest toxicity on healthy mammalian cells (V79, hamster lung and MDCK, dog kidney). This is the first report on the effect of calix(n)arenes as growth inhibitors of Paracoccidioides fungi.

From Nature to Market: Examples of Natural Products that Became Drugs

Nature is an irrefutable source of inspiration for the modern man in many aspects. The observation and understanding of nature have allowed the development of new materials, new sources of energies, new drugs etc. Specifically, natural products provide a great contribution to the development of new agents for the treatment of infections and antitumor agents. However, obtaining natural products directly from animals, fungi, bacteria, plants etc has been considered not enough to attend the high demand by pharmaceutical industries. In this regard, various strategies based on biotechnological processes or synthetic approaches have been developed. In this scenario the total synthesis can be undoubtedly a useful and powerful tool for obtaining higher amounts of natural products and/or structural modifications thereof. Herein, we emphasize successful examples of total synthesis of galanthamine, morphine, paclitaxel and podophyllotoxin - natural products approved as pharmaceuticals.

Biological activities of eco-friendly synthesized Hantzsch adducts.

Fourteen Hantzsch adducts with different substituents at the C-4 position were synthesized through multicomponent reactions by using citric or lactic acid as catalysts. To the best of our knowledge, this is the first report on the synthesis of such a class of compounds based on multicomponent reactions catalyzed by non-toxic organic acids. The potential to scavenge reactive nitrogen/oxygen species (RNS/ROS) and the ability to inhibit cancer cell growth were then investigated. Among the synthesized compounds, adduct 15 was the most promising free radical scavenger, while adduct 20 was shown to have a wider spectrum of action on the cancer cells studied. These results highlight Hantzsch adducts as lead compounds for obtaining new free radical scavengers and anticancer agents.

Organocatalysis in the Three-Component Povarov Reaction and Mechanistic Investigation by Mass Spectrometry

The advent of organocatalysis brought the prospect of a complementary mode of catalysis, with the potential for savings in cost, time and energy. 1 In this work p-sulfonic acid calix[4]arene (CX4SO3H) was employed as a organocatalyst to promote a threecomponent Povarov reaction, for the preparation of julolidines. 2 Julolidines and derivatives are endowed with interesting scientific and industrial applications. 3