Review Article; Anticancer Activities of Some Fused Heterocyclic Moieties Containing Nitrogen and/or Sulfur Heteroatoms

Abstract

Cancer cells often have a high demand for antiapoptotic proteins in order to resist programmed cell death. Heterocyclic compounds present themselves as a fundamental division of organic chemistry. Most clinically effective antitumor agents are inhibitors of DNA, RNA or protein synthesis, enzyme inhibition and/or interfere with the metabolism of other cell components, frequently lacking or displaying poor selective antitumor activity. The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique physicochemical properties have poised them as true cornerstones of medicinal chemistry. The S-heterocyclic core (Thiophene) has been reported to possess significant importance in various fields from medicinal chemistry. Many diverse biologically active products were prepared, several of which exhibited antimicrobial, analgesic, anti-inflammatory, antioxidant, antitumor, local anesthetic, anticoagulant and antithrombotic activities. Many N-heterocyclic compounds that are broadly distributed in Nature, possess physiological and pharmacological properties and are constituents of many biologically important molecules, including many vitamins, nucleic acids, pharmaceuticals, antibiotics, dyes and agrochemicals, amongst many others. The base pairs of DNA and RNA (Guanine, cytosine, adenine, and thymine) are also made up of N-heterocyclic compounds, namely purines, pyrimidines, etc. These nitrogen-containing heterocyclic molecules with distinct characteristics and applications have gained prominence in the rapidly expanding fields of organic and medicinal chemistry and the pharmaceutical industry. Finally, many of these compounds have higher activity against cancer cells using the standard MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)assay.

Design of Novel Enantiopure Dispirooxindolopyrrolidine-Piperidones as Promising Candidates toward COVID-19: Asymmetric Synthesis, Crystal Structure and In Silico Studies

“…Crystal data for C 41 H 41 N 3 O 6 , M = 671.77 g•mol −1 , dark orange crystals, crystal size 0.781 × 0.534 × 0.378 mm 3 , monoclinic, space group P2 1 , a = 11.6919(4) Å, b = 22.6612(7) Å, c = 13.0938(4) Å), α = 90 • , β = 90.3920 (10) • , γ = 90; V = 3469.15(19) Å 3 , Z = 4, D calc = 1.286 g/cm 3 , T = 100 K, R 1 = 0.0296, wR 2 = 0.0749 for 45555 reflections with I > = 2σ (I) and 14594 independent reflections. Largest diff.…”

“…Nitrogen-based heterocycles represent a major key structural basis for numerous commercialized approved drugs [9]. The unique physicochemical properties of these heterocycles have garnered increased attention in designing and synthesizing new molecules, several of which display significant biological activities [10][11][12][13][14][15][16][17]. Recently, several libraries of N-heterocyclic compounds have been prepared and assessed for their anti-SARS-CoV-2 activities [18][19][20], resulting in a considerable number of drug candidates currently in clinical trials [21,22].…”

Oxidative Cyclization of 4‐(2‐Mercaptophenyl)‐Substituted 4H‐1,2,4‐Triazolium Species to Tricyclic Benzothiazolium Salts

“…The vast majority of biologically active molecules found in pharmaceuticals and agrochemicals bear at least one heterocyclic ring [1–6] . Of particular interest are compounds based on fused heterocyclic scaffolds which exhibit a wide range of biological activity [7–10] . Among these molecules are several fused nitrogen‐ and sulfur‐containing heterocyclic anti‐cancer agents incorporating a (benzo)thiazole fragment, [10–22] a thiadiazole ring, [23–28] or a thiadiazine unit [27–29] .…”

“…[1][2][3][4][5][6] Of particular interest are compounds based on fused heterocyclic scaffolds which exhibit a wide range of biological activity. [7][8][9][10] Among these molecules are several fused nitrogen-and sulfur-containing heterocyclic anti-cancer agents incorporating a (benzo)thiazole fragment, [10][11][12][13][14][15][16][17][18][19][20][21][22] a thiadiazole ring, [23][24][25][26][27][28] or a thiadiazine unit. [27][28][29] The same scaffolds can be found in molecules with antibacterial, antimicrobial and antifungal properties, [22,[30][31][32][33][34][35] prospective therapeutic agents used to treat asthma or chronic obstructive pulmonary disease, [36][37][38] molecules with anti-inflammatory activity, [39] compounds with antidiabetic activity, [40,41] and promising therapeutics to treat Alzheimer's disease…”

Computational study of heterocyclic anticancer compounds through nbo method

“…The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique physicochemical properties, have poised them as true cornerstones of medicinal chemistry. (Jia, Bonaventura, Bonaventura, & Stamler, 1996;Martins et al, 2015;Omar, 2020) To date, a new generation of molecularly targeted drugs is eagerly expected whose rational for suggestion new structure for anticancer drug or other type of drugs to investigate the activity to binding DNA or cancer cell. In recent years Computation study in biological field specially on drugs and interaction with DNA attract the research attention (Kruszewski & Krygowski, 1972) .in our previous report we have optimized and discussed about several active compounds which are shoed anticancer activity through NMR study and NICS and S-NICS study.…”