Nitrogen Containing Heterocycles as Anticancer Agents: A Medicinal Chemistry Perspective

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(2), P. 299 - 299

Published: Feb. 14, 2023

Cancer is one of the major healthcare challenges across globe. Several anticancer drugs are available on market but they either lack specificity or have poor safety, severe side effects, and suffer from resistance. So, there a dire need to develop safer target-specific drugs. More than 85% all physiologically active pharmaceuticals heterocycles contain at least heteroatom. Nitrogen constituting most common heterocyclic framework. In this study, we compiled FDA approved with nitrogen atoms their pharmacological properties. Moreover, reported containing heterocycles, including pyrimidine, quinolone, carbazole, pyridine, imidazole, benzimidazole, triazole, β-lactam, indole, pyrazole, quinazoline, quinoxaline, isatin, pyrrolo-benzodiazepines, pyrido[2,3-d]pyrimidines, which used in treatment different types cancer, concurrently covering biochemical mechanisms action cellular targets.

Language: Английский

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Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids

Pharmaceuticals, Journal Year: 2022, Volume and Issue: 15(9), P. 1071 - 1071

Published: Aug. 28, 2022

Cancer is a complex disease, and its treatment big challenge, with variable efficacy of conventional anticancer drugs. A two-drug cocktail hybrid approach potential strategy in recent drug discovery that involves the combination two pharmacophores into single molecule. The molecule acts through distinct modes action on several targets at given time more less susceptibility to resistance. Thus, there huge scope for using compounds tackle present difficulties cancer medicine. Recent work has applied this technique uncover some interesting molecules substantial properties. In study, we report data numerous promising anti-proliferative/anti-tumor agents developed over previous 10 years (2011–2021). It includes quinazoline, indole, carbazole, pyrimidine, quinoline, quinone, imidazole, selenium, platinum, hydroxamic acid, ferrocene, curcumin, triazole, benzimidazole, isatin, pyrrolo benzodiazepine (PBD), chalcone, coumarin, nitrogen mustard, pyrazole, pyridine-based hybrids produced via molecular hybridization techniques. Overall, review offers clear indication benefits merging pharmacophoric subunits from multiple different known chemical prototypes produce potent precise compounds. This provides valuable knowledge researchers working diseases such as cancer.

Language: Английский

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Benzimidazole and its derivatives: Recent Advances (2020–2022)

Results in Chemistry, Journal Year: 2023, Volume and Issue: 5, P. 100925 - 100925

Published: Jan. 1, 2023

Benzimidazoles are fused heterocyclic ring systems containing two nitrogen atoms. They have vital therapeutic significance in drug discovery. Many clinically approved drugs been developed from benzimidazole, and these include liarozole pracinostat (anticancer), omeprazole (proton pump inhibitors), oxfendazole (Anthelmintic), enviroxine (antiviral), ilaprazole (antiulcer), ridinilazole (antibacterial), flubendazole (antiparasitic), bilastine (antihistaminic), many more. The vast applications of benzimidazole its derivatives propelled researchers to develop more biologically active compounds bearing thus broadening the scope finding a remedy for other diseases; as result, new pharmaceutical expected be available within next decade. In this review, we describe bioactive hybrids recent year, 2020 2022, accentuate pros using development.

Language: Английский

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Benzimidazole based derivatives as anticancer agents: Structure activity relationship analysis for various targets

Journal of Heterocyclic Chemistry, Journal Year: 2021, Volume and Issue: 59(1), P. 22 - 66

Published: Aug. 28, 2021

Abstract Benzimidazole, the benzo derivative of imidazole, is a class bicyclic aromatic organic compound consisting six‐membered benzene ring fused to five‐membered imidazole at 4‐ and 5‐positions ring. It vital pharmacophore many biologically active heterocyclic compounds with variety pharmacological activities. Over time, benzimidazole its derivatives have evolved as vibrant systems due their potency in wide range bioactive like analgesics, antifungals, anti‐inflammatory, antihypertensives, proton pump inhibitors, anti‐HIV, antiviral, so on. Multi‐drug resistance cancer that led failure chemotherapeutic drugs major concern. Various approaches are being developed overcome this problem. One them target based drug discovery, which an effective method develop novel anticancer drug. To newer drugs, previously reported work needs be studied. Keeping mind, last 5 years literature on used agents has been reviewed summarized paper herein. This review article along also deal structure activity relationship various having

Language: Английский

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Design, synthesis, molecular modeling, DFT, ADME and biological evaluation studies of some new 1,3,4-oxadiazole linked benzimidazoles as anticancer agents and aromatase inhibitors

Journal of Biomolecular Structure and Dynamics, Journal Year: 2022, Volume and Issue: 41(5), P. 1944 - 1958

Published: Jan. 17, 2022

Breast cancer is the most frequent female and second cause of cancer-related deaths among women around world. Two thirds breast patients have hormone-dependent tumors, which very likely be treated with hormonal therapy. Aromatase involved in biosynthesis estrogen thus a critical target for cancer. In this study, order to identify new aromatase enzyme inhibitors, series benzimidazole-1,3,4-oxadiazole derivatives were synthesized characterized by 1H NMR, 13C MS spectra analyses. vitro anticancer assay, all compounds tested activities using MTT-based assay against five cell lines (MCF-7, A549, HeLa, C6, HepG2). Among them, compound 5a exhibited potent activity IC50 values 5.165 ± 0.211 μM 5.995 0.264 MCF-7 HepG2 lines. Compound was included BrdU test determine DNA synthesis inhibition effects both types. Furthermore, 5c also found more effective than doxorubicin on HeLa line. The selectivity evaluated NIH3T3 vitro, enzymatic assays performed acting For 5a, silico molecular docking dynamics simulations possible protein-ligand interactions stability. DFT study evaluate quantum mechanical electronic properties 5a. Finally, theoretical ADME potential inhibitor analyzed calculations.Communicated Ramaswamy H. Sarma

Language: Английский

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A Mini Review on Isatin, an Anticancer Scaffold with Potential Activities against Neglected Tropical Diseases (NTDs)

Pharmaceuticals, Journal Year: 2022, Volume and Issue: 15(5), P. 536 - 536

Published: April 27, 2022

Isatin, chemically an indole-1H-2,3-dione, is recognised as one of the most attractive therapeutic fragments in drug design and development. The template has turned out to be exceptionally useful for developing new anticancer scaffolds, evidenced by increasing number isatin-based molecules which are either clinical use or trials. Apart from its promising antiproliferative properties, isatin shown potential treating Neglected Tropical Diseases (NTDs) not only a parent core, but also attenuating activities various pharmacophores. objective this mini-review keep readers up date on latest developments biological targeting cancer NTDs such tuberculosis, malaria, microbial infections.

Language: Английский

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Discovery of new nicotinamides as apoptotic VEGFR-2 inhibitors: virtual screening, synthesis, anti-proliferative, immunomodulatory, ADMET, toxicity, and molecular dynamic simulation studies

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 37(1), P. 1389 - 1403

Published: May 16, 2022

A library of modified VEGFR-2 inhibitors was designed as inhibitors. Virtual screening conducted for the hypothetical using in silico docking, ADMET, and toxicity studies. Four compounds exhibited high affinity against an acceptable range drug-likeness. These were synthesised subjected to vitro cytotoxicity assay two cancer cell lines besides inhibitory determination. Compound D-1 showed cytotoxic activity HCT-116 cells almost double that sorafenib. Compounds A-1, C-6, good IC50 values VEGFR-2. markedly increased levels caspase-8 BAX expression decreased anti-apoptotic Bcl-2 level. Additionally, compound caused cycle arrest at pre-G1 G2-M phases induced apoptosis both early late apoptotic stages. level TNF-α IL6 inhibited IL6. MD simulations studies performed over 100 ns.

Language: Английский

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Discovery of new quinoline and isatine derivatives as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative, docking and MD simulation studies

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: 41(21), P. 11535 - 11550

Published: Jan. 8, 2023

A new set of quinoline and isatine derivatives were synthesized as antiangiogenic VEGFR-2 inhibitors. On a biological level, the in vitro ability obtained candidates to inhibit was found be strong with IC50 values range 76.64-175.50 nM. To investigate cytotoxicity safety, all compounds tested against panel four cancer cell lines (A549, Caco2, HepG2 MDA) well two normal (Vero WI-38). Interestingly, compound 12 exhibited noticeable A549, Caco2 MDA 5.40, 0.58 0.94 µM, respectively. These results better comparable that doxorubicin (0.70, 0.82 0.90 respectively) more than three folds higher selectivity index lines. Compound 9 prevented healing cells at low concentration. Also, compound's potential induce programmed death Caco-2 proved through significant down regulating expression Bcl2, Bcl-xl Survivin addition slight upregulation TGF-β gene. The cycle analysis indicated arrested G2/M phase. molecular docking studies revealed correct binding targeted similar sorafenib. Furthermore, MD experiments validated over 100 ns, MM-PBSA confirmed precise optimum energy. Finally, ADMET showed general drug-likeness safety compounds.Communicated by Ramaswamy H. Sarma.

Language: Английский

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Novel 4-thiophenyl-pyrazole, pyridine, and pyrimidine derivatives as potential antitumor candidates targeting both EGFR and VEGFR-2; design, synthesis, biological evaluations, andin silicostudies

RSC Advances, Journal Year: 2023, Volume and Issue: 13(18), P. 12184 - 12203

Published: Jan. 1, 2023

In this article, we continued our previous effort to develop new selective anticancer candidates based on the basic pharmacophoric requirements of both EGFR and VEGFR-2 inhibitors. Therefore, twenty-two novel 4-thiophenyl-pyrazole, pyridine, pyrimidine derivatives were designed examined as dual EGFR/VEGFR-2 Besides, previously reported antimicrobial activities aforementioned nuclei motivated us screen their antibacterial antifungal well. First, antitumor newly synthesized evaluated against two cancer cell lines (HepG-2 MCF-7). Notably, compounds 2a, 6a, 7a, 10b, 15a, 18a exhibited superior HepG-2 MCF-7 lines. These selected further evaluate anti-EGFR anti-VEGFR-2 potentialities which found be very promising compared erlotinib sorafenib, respectively. Both 10b 2a achieved better inhibition with IC50 values 0.161 0.141 μM 0.209 0.195 μM, Moreover, most active was exact phase cycle arrest investigate mechanism death whether it due apoptosis or necrosis. On other hand, all tested Gram-positive bacteria such S. aureus B. subtilis well Gram-negative E. coli P. aeuroginosa. Also, activity investigated C. albicans A. flavus strains. The findings tests revealed that strong moderate effects. Furthermore, understand pattern by bound site, subjected different docking processes into binding sites. tried correlate compound reference drugs (erlotinib sorafenib) through DFT calculations. Finally, following biological data pyrazole, candidates, concluded a interesting SAR for optimization.

Language: Английский

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Discovery of indolinone-bearing benzenesulfonamides as new dual carbonic anhydrase and VEGFR-2 inhibitors possessing anticancer and pro-apoptotic properties

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 259, P. 115707 - 115707

Published: Aug. 2, 2023

Language: Английский

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