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  • 1
    Online Resource
    Online Resource
    Mediterranean Journal of Chemistry ; 2023
    In:  Mediterranean Journal of Chemistry Vol. 13, No. 2 ( 2023-04-20), p. 156-
    In: Mediterranean Journal of Chemistry, Mediterranean Journal of Chemistry, Vol. 13, No. 2 ( 2023-04-20), p. 156-
    Abstract: : 〈 strong 〉 〈 /strong 〉 Cancer is one of the fastest-growing epidemics that affect millions yearly. A handful of anticancer drugs are available on the market, but they produce undesirable side effects. Currently, tubulin inhibitors targeting the colchicine binding site are considered an important target due to their structural simplicity and favorable pharmacokinetics with fewer side effects. Different researchers conducted many studies to discover a novel tubulin inhibitor targeting the colchicine binding site with high safety and potency. In the present study, we performed computational analysis of 48 styrylquinolines analogs obtained from literature using different drug designing tools. The pharmacophore mapping study was conducted to identify the important pharmacophoric features essential for biological activity. Atom-based 3D-QSAR (3-dimensional quantitative structure-activity relationship) analysis was carried out to know the contribution of different atoms to model development. The generated model showed a statistically significant coefficient of determinations for the training and test sets. The best QSAR model was selected based on R 〈 sup 〉 2 〈 /sup 〉 (0.8624) and Q 〈 sup 〉 2 〈 /sup 〉 (0.6707) values. Contour plot analysis of the developed model unveiled the chemical features necessary for tubulin inhibition. A docking study was performed on potent styrylquinoline analog 9VII-f(46), which shows the highest SP docking scores (-5.494). ADME (Absorption, distribution, metabolism, and excretion) analysis provides valuable information about the drugability of newly designed compounds.
    Type of Medium: Online Resource
    ISSN: 2028-3997
    Language: Unknown
    Publisher: Mediterranean Journal of Chemistry
    Publication Date: 2023
    detail.hit.zdb_id: 2735401-5
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  • 2
    In: Journal of Molecular Structure, Elsevier BV, Vol. 1227 ( 2021-03), p. 129511-
    Type of Medium: Online Resource
    ISSN: 0022-2860
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1491504-2
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  • 3
    Online Resource
    Online Resource
    Informa UK Limited ; 2022
    In:  Journal of Biomolecular Structure and Dynamics Vol. 40, No. 20 ( 2022-11-29), p. 10422-10436
    In: Journal of Biomolecular Structure and Dynamics, Informa UK Limited, Vol. 40, No. 20 ( 2022-11-29), p. 10422-10436
    Type of Medium: Online Resource
    ISSN: 0739-1102 , 1538-0254
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2085732-9
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2022
    In:  In Silico Pharmacology Vol. 10, No. 1 ( 2022-04-08)
    In: In Silico Pharmacology, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2022-04-08)
    Type of Medium: Online Resource
    ISSN: 2193-9616
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2702993-1
    SSG: 15,3
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  • 5
    In: Current Signal Transduction Therapy, Bentham Science Publishers Ltd., Vol. 17, No. 1 ( 2022-04), p. 12-58
    Abstract: The development of multi-resistant strains of the Plasmodium parasite has become a global problem. Therefore, designing of new antimalarial agents is an exclusive solution. Objective: To improve the activity and identify potentially efficacious new antimalarial agents, integrated computational perspectives such as pharmacophore mapping, 3D-QSAR and docking study have been applied to a series of indolo-quinoline derivatives. Methods: The pharmacophore mapping generated various hypotheses based on key functional features and the best hypothesis ADRRR_1 revealed that indolo-quinoline scaffold is essential for antimalarial activity. 3D-QSAR model was established based on CoMFA and CoMSIA models by using 30 indolo-quinoline analogues as training set and the rest of 19 as test set. Results: The molecular field analysis (MFA) with PLS (partial least-squares) method was used to develop significant CoMFA (q2=0.756, r2=0.996) and CoMSIA (q2=0.703, r2=0.812) models. The CoMFA and CoMSIA models showed good predictive ability with r2 pred values of 0.9623 and 0.9214 respectively. Docking studies were performed by using pfLDH to identify structural insight into the active site and results signify that the quinoline nitrogen acts as a hydrogen bond acceptor region to facilitate interaction with Glu122. Finally, designed molecules were screened through the ADMET tool to evaluate the pharmacokinetic and drug-likeness parameters. Conclusion: Thus, these studies suggested that established models have good predictability and would help in the optimization of newly designed molecules that may produce potent antimalarial activity.
    Type of Medium: Online Resource
    ISSN: 1574-3624
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2022
    SSG: 12
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  • 6
    In: Current Signal Transduction Therapy, Bentham Science Publishers Ltd., Vol. 18, No. 1 ( 2023-03)
    Abstract: The prolonged antimalarial therapy with the marketed drug has developed multi-resistant strains of Plasmodium parasites that emerge as a consequential global problem. Therefore, designing new antimalarial agents is an exclusive solution to overcome the alarming situation. Methods: The integrated computational perspectives, such as pharmacophore mapping, 3D-QSAR and docking studies have been applied to improve the activity of the imidazo-quinoline scaffold. The best hypothesis AARRR_1 (Survival score 5.4609) obtained through pharmacophore mapping revealed that imidazo-quinoline scaffold is found to be vital for antimalarial activity. The significant CoMFA (q2 = 0.728, r2 = 0.909) and CoMSIA (q2 = 0.633, r2 = 0.729) models, developed by using molecular field analysis with the PLS method, showed good predictive ability with r2 pred values of 0.9127 and 0.7726, respectively. Docking studies were performed using Schrodinger and GOLD software with the Plasmodium falciparum purine nucleoside phosphorylase enzyme (PDB ID-5ZNC) and results indicated that the imidazo-quinoline moiety facilitates the interaction with Tyr 160. Results: In addition, some compounds are screened from the ZINC database based on structural requirements to verify the relevance of the research. Finally, designed molecules and ZINC database compounds were screened through the ADMET tool to evaluate pharmacokinetic and druglikeness parameters. Conclusion: Thus, these exhaustive studies suggested that established models have good predictability and would help in the optimization of newly designed molecules that may lead to potent antimalarial activity for getting rid of resistance issues.
    Type of Medium: Online Resource
    ISSN: 1574-3624
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2023
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Bentham Science Publishers Ltd. ; 2023
    In:  Mini-Reviews in Medicinal Chemistry Vol. 23, No. 1 ( 2023-01), p. 33-52
    In: Mini-Reviews in Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 23, No. 1 ( 2023-01), p. 33-52
    Abstract: Cancer is the main cause of death and the most significant determinant of life expectancy in every country in the twenty-first century. According to the World Health Organization (WHO) cancer is responsible for major cause of death globally. Benzophenone derivatives are found in a variety of naturally occurring compounds which are known to be pharmacologically efficacious against a variety of diseases, including cancer. Microtubules are thought to be a good target for cancer chemotherapies. Microtubule polymerization and depolymerization are induced by a variety of natural, synthetic, and semisynthetic chemicals having a benzophenone nucleus, affecting tubulin dynamics. Several medications that affect microtubule dynamics are in various stages of clinical trials, including Combretastatins (phase II), Vincristine (clinically approved), Paclitaxel (in clinical usage), and epothilone (phase III), and only a few have been patented. Benzophenone derivatives act by targeting the colchicine binding site of microtubules damage them and cause cell cycle arrest in the G2-M phase. Belonging to this class of molecules, phenstatin, a potent inhibitor of tubulin polymerization, shown strongly inhibited cancer cell growth and arrest the G2/M phase of the cell cycle by targeting the colchicine binding site of microtubules. In the present manuscript we described the benzophenone as tubulin polymerization inhibitors their structure activity relationships (SARs) and molecular docking studies that reveal its binding affinity with the colchicine binding site.
    Type of Medium: Online Resource
    ISSN: 1389-5575
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2023
    SSG: 15,3
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  • 8
    Online Resource
    Online Resource
    Bentham Science Publishers Ltd. ; 2023
    In:  Mini-Reviews in Medicinal Chemistry Vol. 23, No. 21 ( 2023-11), p. 2008-2040
    In: Mini-Reviews in Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 23, No. 21 ( 2023-11), p. 2008-2040
    Abstract: Diabetes Mellitus (DM) is a long-term metabolic condition that is characterized by excessive blood glucose. DM is the third most death-causing disease, leading to retinopathy, nephropathy, loss of vision, stroke, and cardiac arrest. Around 90% of the total cases of diabetic patients have Type II Diabetes Mellitus (T2DM). Among various approaches for the treatment of T2DM. G proteincoupled receptors (GPCRs) 119 have been identified as a new pharmacological target. GPR119 is distributed preferentially in the pancreas β-cells and gastrointestinal tract (enteroendocrine cells) in humans. GPR119 receptor activation elevates the release of incretin hormones such as Glucagon-Like Peptide (GLP1) and Glucose Dependent Insulinotropic Polypeptide (GIP) from intestinal K and L cells. GPR119 receptor agonists stimulate intracellular cAMP production via Gαs coupling to adenylate cyclase. GPR119 has been linked to the control of insulin release by pancreatic β-cells, as well as the generation of GLP-1 by enteroendocrine cells in the gut, as per in vitro assays. The dual role of the GPR119 receptor agonist in the treatment of T2DM leads to the development of a novel prospective anti-diabetic drug and is thought to have decreased the probability of inducing hypoglycemia. GPR119 receptor agonists exert their effects in one of two ways: either by promoting glucose absorption by β-cells, or by inhibiting α-cells' ability to produce glucose. In this review, we summarized potential targets for the treatment of T2DM with special reference to GPR119 along with its pharmacological effects, several endogenous as well as exogenous agonists, and its pyrimidine nucleus containing synthetic ligands.
    Type of Medium: Online Resource
    ISSN: 1389-5575
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2023
    SSG: 15,3
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