Letters in Organic Chemistry - Volume 18, Issue 4, 2021

Natural products play an important role in various drug discovery and development approaches. They are known to be the rich resources for the identification of new chemical entities (NCEs) intended to treat various diseases. Many drugs have been discovered and developed from natural sources. Indeed, collaborative efforts involving biologists as well as organic, medicinal, and phytochemists usually facilitate the identification of potent NCEs derived from natural sources. Over the past 20 years, more than 50% of NCEs have been derived either from marine sources or synthetic/ semisynthetic derivatives of natural products. Indeed, many drug molecules have been designed by considering natural products as the starting scaffold. The first bis-pyrrole alkaloid derivative of marinopyrroles was obtained from the marine-derived streptomycete species. In the laboratory, it can be synthesized via Clauson-Kaas and Friedel-Crafts arylation as well as copper-mediated N-arylation process under microwave irradiation. The marinopyrrole A (±)-28 was discovered to overcome resistance against human cancer cells by antagonizing B-cell lymphoma extra-large (Bcl-xL) and induced myeloid leukaemia cell (Mcl-1). In this review, we elaborated on various synthetic pathways of marinopyrroles possessing anti-cancer potential, which could encourage researchers to discover promising anti-tumor agents.

A series of novel quinoline derivatives (6-phenyl-6H-chromeno[4,3-b]quinoline) have been prepared by using 4-chloro-2-phenyl-2H-chromene-3-carbaldehyde and various substituted isocyanides as starting materials in the presence of HClO4-SiO2 and Methanol. We screened eighteen compounds of this novel series (6a-r) in six different cancer cell lines (A549 (lung cancer cells), DU145 (prostate cancer cells), PC3 (prostate cancer cells), MCF7 (lung cancer cells), HT 29, HCT 116 (colon cancer cells). Most of the compounds showed anti-cancer activity and compound 6b showed good cytotoxicity IC50 = 2.61±0.34 μM against colon cancer on HT29 cell line among all. The key property of cell migration was observed while treatment cells with 6b. Apoptosis in HT29 cells confirmed by annexin V staining, acridine orange/ethidium bromide (AO/EB), DAPI, induced by 6b. This method is operationally simple and works with a diverse range of substrates. These results indicate the anticancer potential of these series and warrants future investigations for further anticancer drug development.

Multi-component synthesis of functionalized pyrrole derivatives was achieved via a fourcomponent condensation reaction of ethyl acetoacetate/ methyl acetoacetate, aromatic amines, nitromethane, and aromatic aldehydes using triethanolammonium acetate ([TEAH][OAc]) ionic liquid as a green solvent and catalyst. Easy access to highly substituted pyrroles, reusability of the catalyst, broad substrate scopes, no column chromatography, short reaction time, good yields of products and solventfree conditions make this protocol environmentally friendly and practically attractive.

Cissus aralioides is a medicinal plant used in sub-Saharan Africa for the treatment of infectious diseases; however, the chemical constituents of the plant have not been investigated. Thus, in this study, an attempt was made at identifying predominant phytochemical constituents of the plant through chromatographic purification and silylation of the plant extract, and subsequent characterization using spectroscopic and GC-MS techniques. The minimum inhibitory concentration (MICs) for the antibacterial activities of the plant extract, chromatographic fractions, and isolated compounds were also examined. Chromatographic purification of the ethyl acetate fraction from the whole plant afforded three compounds: β-sitosterol (1), stigmasterol (2), and friedelin (3). The phytosterols (1 and 2) were obtained together as a mixture. The GC-MS analysis of silylated extract indicated alcohols, fatty acids, and sugars as predominant classes, with a composition of 24.62, 36.90 and 26.52%, respectively. Results of MICs indicated that friedelin and other chromatographic fractions had values (0.0626-1.0 mg/mL) comparable with the standard antibiotics used. Characterization of natural products from C. aralioides is being reported for the first time in this study.

The applications of a new supported tribromide reagent (poly(vinylbenzyltrimethylammonium tribromide) resin) were reported. This supported tribromide resin was used as a catalyst in the acetalization and diacetylation of benzaldehydes under mild conditions with high efficiency. The effects of solvents, and amount of the supported tribromide resin on the reactions were investigated. Under the optimal conditions, most of acetal and 1,1-diacetates of benzaldehydes were selectively obtained in excellent yields.

1-Butyl-3-methylimidazolium hydrogen sulfate [bmim]HSO4 as a non-halogenated ionic liquid was loaded on graphene oxide ([bmim]HSO4/GO) and employed as a green, reusable, solid nanocatalyst for the preparation of polysubstituted pyrroles in the presence of amines (such as benzeneamine, 2-amino-4-methylthiazole, adenine (9H-purin-6-amine)), benzaldehydes or cinnamaldehyde or furfural, 1,3-dicarbonyl compounds, and nitromethane at 90-95°C. The advantages of this protocol are the synthesis of some novel polysubstituted pyrroles containing fluorine atoms, thiazole and adenine nuclei that are very important in pharmaceutical and drug discovery research in comparison to previously reported results.

As infectious diseases causing bacteria and fungi are developing resistance to existing antimicrobial drugs, it is necessary to search for new drug targets with different structures and modes of action. Hence, it is essential to screen for new antimicrobial drugs with good efficacy and less toxicity. The reaction of 2-amino benzimidazoles 1 with ethyl cyanoacetate 2 afforded N-(1H-benzo[d]imidazol-2-yl)-2- cyanoacetamides 3. Compounds 3 on Knoevenagel condensation with o-nitro benzaldehydes 4 produced (E)-N-(1H-benzo[d]imidazol-2-yl)-2-cyano-3-(2-nitrophenol) acylamides 5. Compounds 5 were converted to 2-amino -N-(1H-benzo[d]imidazol-2-yl) quinoline-3-carboxamides 6 on treatment with stannous chloride by reductive cyclization. The target compounds viz., 3-(1H-benzo[d]imidazol-2-yl)-2- methylpyrimido [4, 5-b] quinolin-4(3H)-ones 7 were obtained by N-acetylation followed by cyclodehydration of compounds 6 in situ by treatment with acetic anhydride. 3-(1H-Benzo[d]imidazol-2-yl)-2- methylpyrimido [4, 5-b] quinolin-4(3H)-ones 7 have been synthesized from commercially available materials in excellent yields. The title compounds 7a-h are evaluated for in vitro antimicrobial activity. Compounds 7e, 7f and 7h have shown more antimicrobial activity than that of standard drugs. The structures of all the newly synthesized compounds 3, 5, 6 & 7 are confirmed on the basis of spectral data. Antimicrobial studies of compounds 7a-h have revealed that compounds 7e and 7f have more efficient activity when compared to the standard drugs.

Based on 4,6-dimethylpyrimidine-2-thiol hydrochloride a series of its novel S-substituted derivatives including bi- and tricyclic heterosystems with a combination of azines and pyrazole cycles in the molecule were synthesized. The preliminary biological screening has shown that the obtained compounds have a pronounced plants growth-stimulating activity, which is a new property for these heterosystems. This fact indicates the prospectivity of further development of synthesized systems for the search for new plants growth stimulators.

An efficient, green and rapid protocol for one-pot synthesis of substituted imidazoles from isatin, aryl/hetero-aryl aldehydes and ammonium acetate in presence of CuO-TiO2-GO nanocomposite as catalyst under microwave irradiation has been reported in this article. The CuO-TiO2-GO nanocomposite was synthesized by the hydrothermal method. Further, the prepared composite was characterized by FT-IR, XRD, FESEM, EDS, TEM, Raman and TGA techniques. The protocol offered several advantages such as high rate of reaction, excellent yields, economic feasibility, simple work-up and reusability of catalyst up to six cycles. Further antimicrobial activities of the synthesized substituted imidazoles were evaluated by the broth dilution method.