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1.
Russ J Bioorg Chem ; 49(2): 157-166, 2023.
Article in English | MEDLINE | ID: mdl-36852389

ABSTRACT

Drug repurposing is using an existing drug for a new treatment that was not indicated before. It has received immense attention during the COVID-19 pandemic emergency. Drug repurposing has become the need of time to fasten the drug discovery process and find quicker solutions to the over-exerted healthcare scenario and drug needs. Drug repurposing involves identifying the drug, evaluating its efficiency using preclinical models, and proceeding to phase II clinical trials. Identification of the drug candidate can be made through computational and experimental approaches. This approach usually utilizes public databases for drugs. Data from primary and translational research, clinical trials, anecdotal reports regarding off-label uses, and other published human data information available are included. Using artificial intelligence algorithms and other bioinformatics tools, investigators systematically try to identify the interaction between drugs and protein targets. It can be combined with genetic data, clinical analysis, structure (molecular docking), pathways, signatures, targets, phenotypes, binding assays, and artificial intelligence to get an optimum outcome in repurposing. This article describes the strategies involved in drug repurposing and enlists a series of repurposed drugs and their indications.

2.
Curr Med Chem ; 18(10): 1488-508, 2011.
Article in English | MEDLINE | ID: mdl-21428893

ABSTRACT

Quinoline (1-azanaphthalene) is a heterocyclic aromatic nitrogen compound characterized by a double-ring structure that contains a benzene ring fused to pyridine at two adjacent carbon atoms. Quinoline compounds are widely used as "parental" compounds to synthesize molecules with medical benefits, especially with anti-malarial and anti-microbial activities. Certain quinoline-based compounds also show effective anticancer activity. This broad spectrum of biological and biochemical activities has been further facilitated by the synthetic versatility of quinoline, which allows the generation of a large number of structurally diverse derivatives. This includes numerous analogues derived from substitution of the quinoline ring system, and derivatization of quinoline ring structure. Quinoline and its analogs have recently been examined for their modes of function in the inhibition of tyrosine kinases, proteasome, tubulin polymerization and DNA repair. In this review, we have summarized our knowledge on quinoline compounds with respect to their anticancer activities, mechanisms of action, structure-activity relationship (SAR), and selective and specific activity against various cancer drug targets. In particular, we focus our review on in vitro and in vivo anticancer activities of quinoline and its analogs in the context of cancer drug development and refinement.


Subject(s)
Neoplasms/drug therapy , Quinolines/pharmacology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Discovery/methods , Humans , Molecular Targeted Therapy/methods , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Quinolines/chemistry , Structure-Activity Relationship
3.
Eur J Med Chem ; 45(11): 4990-6, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20805010

ABSTRACT

A new series of 4-aminoquinoline derivatives have been synthesized and found to be active against both susceptible and resistant strains of Plasmodium falciparum in vitro. Compound 1-[3-(7-chloro-quinolin-4-ylamino)-propyl]-3-cyclopropyl-thiourea (7) exhibited superior in vitro activity against resistant strains of P. falciparum as compared to chloroquine (CQ). All the compounds showed resistance factor between 0.59 and 4.31 as against 5.05 for CQ. Spectroscopic studies suggested that this class of compounds act on heme polymerization target.


Subject(s)
Aminoquinolines/chemical synthesis , Aminoquinolines/pharmacology , Antimalarials/chemical synthesis , Antimalarials/pharmacology , Heme/antagonists & inhibitors , Polymers/chemistry , Animals , Dose-Response Relationship, Drug , Heme/chemistry , Magnetic Resonance Spectroscopy , Plasmodium falciparum/drug effects , Spectrometry, Mass, Fast Atom Bombardment
4.
Eur J Med Chem ; 45(9): 3916-23, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20561720

ABSTRACT

A series of chloroquine (CQ) analogs were designed and synthesized in a repositioning approach to develop compounds with high anti-breast cancer property. The compounds were then examined for their antiproliferative effects on two human breast tumor cell lines and a matching non-cancer cell line. Although many of them showed substantial antiproliferative effects on breast cancer cells examined, two compounds, 7-chloro-N-(3-(4-(7-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)propyl)quinolin-4-amine (14) and {3-[4-(7-chloro-quinolin-4-yl)-piperazin-1-yl]-propyl}-(7-trifluoromethyl-quinolin-4-yl)-amine (26), emerged as the most active among this series. They were particularly potent against MCF7 cells when compared to CQ and cisplatin, a widely prescribed anti-cancer drug. The results suggest that these CQ analogs could serve as bases for the development of a new group of effective cancer chemotherapeutics.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Breast Neoplasms/pathology , Chloroquine/analogs & derivatives , Chloroquine/pharmacology , Drug Design , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/toxicity , Cell Line, Tumor , Cell Proliferation/drug effects , Chloroquine/chemical synthesis , Chloroquine/toxicity , Humans
5.
Bioorg Med Chem ; 15(12): 4009-15, 2007 Jun 15.
Article in English | MEDLINE | ID: mdl-17452107

ABSTRACT

A series of novel 1-substituted-4-benzyl-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones were synthesized by the cyclization of 2-hydrazino-3-benzyl-3H-quinazolin-4-one with various one-carbon donors. The starting material 2-hydrazino-3-benzyl-3H-quinazolin-4-one was synthesized from benzylamine by a new innovative route. When tested for their in vivo H1 -antihistaminic activity on guinea pigs, all the test compounds protected the animals from histamine induced bronchospasm significantly. The compound 1-methyl-4-benzyl-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one (II) emerged as the most active compound of the series and it is more potent (percent protection 76%) when compared to the reference standard chlorpheniramine maleate (percent protection 71%). Compound II showed negligible sedation (7%) when compared to chlorpheniramine maleate (30%). Hence it could serve as prototype molecule for further development as a new class of H1 -antihistamines.


Subject(s)
Histamine H1 Antagonists/chemical synthesis , Histamine H1 Antagonists/pharmacology , Quinazolines/chemical synthesis , Quinazolines/pharmacology , Animals , Guinea Pigs , Histamine H1 Antagonists/chemistry , Magnetic Resonance Spectroscopy , Male , Mice , Quinazolines/chemistry , Spectrophotometry, Infrared
6.
Eur J Med Chem ; 41(11): 1293-300, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16928409

ABSTRACT

A variety of novel 2-methylthio-3-substituted-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-4(3H)-ones have been synthesized by reacting (2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)dithiocarbamic acid methyl ester (5) with a variety of amines. The starting material dithiocarbamate (5) was synthesized from 2-amino-3-carbethoxy-4,5,6,7-tetrahydrobenzo (b) thiophene (1) by a novel innovative route. The title compounds were investigated for analgesic, anti-inflammatory, ulcerogenicity index and antibacterial activities. While the test compounds exhibited significant activity, the compounds 1-methyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A1), 1-dimethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A2), 1-diethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A3) and 1-pyrrolidinyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A4) showed more potent analgesic activity and the compounds 1-dimethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A2), 1-diethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno-[2,3-d]pyrimidin-3-yl)thiourea (A3) and 1-pyrrolidinyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d] pyrimidin-3-yl)thiourea (A4) showed more potent anti-inflammatory activity than the reference standard diclofenac sodium.


Subject(s)
Analgesics/chemical synthesis , Anti-Bacterial Agents/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Pyrimidinones/chemical synthesis , Pyrimidinones/pharmacology , Analgesics/chemistry , Analgesics/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Edema/drug therapy , Female , Magnetic Resonance Spectroscopy , Male , Mass Spectrometry , Mice , Microbial Sensitivity Tests , Pyrimidinones/chemistry , Rats , Rats, Wistar , Spectroscopy, Fourier Transform Infrared , Stomach Ulcer/chemically induced
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