Publications by authors named "Della G T Parambi"

6 Publications

  • Page 1 of 1

Novel Phenolic Compounds as Potential Dual EGFR and COX-2 Inhibitors: Design, Semisynthesis, in vitro Biological Evaluation and in silico Insights.

Drug Des Devel Ther 2021 31;15:2325-2337. Epub 2021 May 31.

Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Aljouf, 72341, Saudi Arabia.

Introduction: Epidermal growth factor receptor (EGFR) inhibition is an imperative therapeutic approach targeting various types of cancer including colorectal, lung, breast, and pancreatic cancer types. Moreover, cyclooxygenase-2 (COX-2) is frequently overexpressed in different types of cancers and has a role in the promotion of malignancy, apoptosis inhibition, and metastasis of tumor cells. Combination therapy has been emerged to improve the therapeutic benefit against cancer and curb intrinsic and acquired resistance.

Methods: Three semi-synthetic series of compounds (, , and ) were prepared and evaluated biologically as potential dual epidermal growth factor receptor (EGFR) and COX-2 inhibitors. The main phenolic constituents of L. (-coumaric, caffeic and gallic) acids have been isolated and subsequently subjected to diazo coupling with various amines to get novel three chemical scaffolds with potential anticancer activities.

Results: Compounds and showed superior inhibitory activity against EGFR (IC: 0.9 and 0.5 µM, respectively) and displayed good COX-2 inhibition (IC: 4.35 and 2.47 µM, respectively). Moreover, the final compounds were further evaluated for their cytotoxic activity against human colon cancer (HT-29), pancreatic cancer (PaCa-2), human malignant melanoma (A375), lung cancer (H-460), and pancreatic ductal cancer (Panc-1) cell lines. Interestingly, compounds and exhibited the highest cytotoxic activity with average IC values of 1.5 µM and 2.8 µM against H-460 and Panc-1, respectively. The virtual docking study was conducted to gain proper understandings of the plausible-binding modes of target compounds within EGFR and COX-2 binding sites.

Discussion: The NMR of prepared compounds showed characteristic peaks that confirmed the structure of the target compounds. The synthesized benzoxazolyl scaffold containing compounds showed inhibitory activities for both COXs and EGFR which are consistent with the virtual docking study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S310820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178614PMC
May 2021

Fascinating Chemopreventive Story of Wogonin: A Chance to Hit on the Head in Cancer Treatment.

Curr Pharm Des 2021 ;27(4):467-478

Division of Drug Design and Medicinal Chemistry Research Lab, Department of Pharmaceutical Chemistry, Ahalia School of Pharmacy, Palakkad, 678557, Kerala, India.

Cancer, global havoc, is a group of debilitating diseases that strikes family as well as society. Cancer cases are drastically increasing these days. Despite many therapies and surgical procedures available, cancer is still difficult to control due to limited effective therapies or targeted therapies. Natural products can produce lesser side effects to the normal cells, which are the major demerit of chemotherapies and radiation. Wogonin, a natural product extracted from the plant, Scutellaria baicalensis has been widely studied and found with a high caliber to tackle most of the cancers via several mechanisms that include intrinsic as well as extrinsic apoptosis signaling pathways, carcinogenesis diminution, telomerase activity inhibition, metastasis inhibition in the inflammatory microenvironment, anti-angiogenesis, cell growth inhibition and arrest of the cell cycle, increased generation of HO and accumulation of Ca and also as an adjuvant along with anticancer drugs. This article discusses the role of wogonin in various cancers, its synergism with various drugs, and the mechanism by which wogonin controls tumor growth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1385272824999200427083040DOI Listing
April 2021

Treatment of Parkinson's Disease by MAO-B Inhibitors, New Therapies and Future Challenges - A Mini-Review.

Comb Chem High Throughput Screen 2020 ;23(9):847-861

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jouf University, Sakaka, Jouf, Saudi Arabia.

Background: One of the most prevalent neurodegenerative diseases with increasing age is Parkinson's disease (PD). Its pathogenesis is unclear and mainly confined to glutamate toxicity and oxidative stress. The dyskinesia and motor fluctuations and neuroprotective potential are the major concerns which are still unmet in PD therapy.

Objective: This article is a capsulization of the role of MAO-B in the treatment of PD, pharmacological properties, safety and efficiency, clinical evidence through random trials, future therapies and challenges.

Conclusion: MAO-B inhibitors are well tolerated for the treatment of PD because of their pharmacokinetic properties and neuroprotective action. Rasagiline and selegiline were recommended molecules for early PD and proven safe and provide a modest to significant rise in motor function, delay the use of levodopa and used in early PD. Moreover, safinamide is antiglutamatergic in action. When added to Levodopa, these molecules significantly reduce the offtime with a considerable improvement of non-motor symptoms. This review also discusses the new approaches in therapy like the use of biomarkers, neurorestorative growth factors, gene therapy, neuroimaging, neural transplantation, and nanotechnology. Clinical evidence illustrated that MAOB inhibitors are recommended as monotherapy and added on therapy to levodopa. A large study and further evidence are required in the field of future therapies to unwind the complexity of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1386207323666200402090557DOI Listing
July 2021

Emerging therapeutic potentials of dual-acting MAO and AChE inhibitors in Alzheimer's and Parkinson's diseases.

Arch Pharm (Weinheim) 2019 Nov 3;352(11):e1900177. Epub 2019 Sep 3.

Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.

No drug has been approved to prevent neuronal cell loss in patients suffering from Parkinson's disease (PD) or Alzheimer's disease (AD); despite increased comprehension of the underlying molecular causes, therapies target cognitive functional improvement and motor fluctuation control. Drug design strategies that adopt the "one protein, one target" philosophy fail to address the multifactorial aetiologies of neurodegenerative disorders such as AD and PD optimally. On the contrary, restoring neurotransmitter levels by combined combinatorial inhibition of cholinesterases, monoamine oxidases, and adenosine A A receptors, in conjunction with strategies to counter oxidative stress and beta-amyloid plaque accumulation, would constitute a therapeutically robust, multitarget approach. This extensive review delineates the therapeutic advantages of combining dual-acting molecules that inhibit monoamine oxidases and cholinesterases and/or adenosine A A receptors, and describes the structure-activity relationships of compound classes that include, but are not limited to, alkaloids, coumarins, chalcones, donepezil-propargylamine conjugates, homoisoflavonoids, resveratrol analogs, hydrazones, and pyrazolines. In the wake of recent advances in network biology, in silico approaches, and omics, this review emphasizes the need to consider conceptually informed research strategies for drug discovery, in the context of the mounting burden posed by chronic neurodegenerative diseases with complex aetiologies and pathophysiologies involving multiple signalling pathways and numerous drug targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ardp.201900177DOI Listing
November 2019

Fe O nanoparticles mediated synthesis of novel spirooxindole-dihydropyrimidinone molecules as Hsp90 inhibitors.

Arch Pharm (Weinheim) 2019 Jan 28;352(1):e1800174. Epub 2018 Nov 28.

Division of Drug Design and Medicinal Chemistry Research Lab, Department of Pharmaceutical Chemistry, Ahalia School of Pharmacy, Palakkad, India.

Heat shock protein 90 (Hsp90) is a validated molecular chaperone considered as the new key recipient for cancer intervention. The current study illustrates the synthesis of novel spirooxindole-dihydropyrimidinones (4a-j) by Fe O nanoparticles intervened synthesis and their Hsp90 ATPase inhibitory activity was investigated by the malachite green assay. All the compounds in the study demonstrated a moderate to potent ATPase inhibitory profile, with IC values ranging from 0.18 to 6.80 μM. Compounds 4j, 4h, 4f, and 4i exhibited maximum inhibitory potential with IC values of 0.18, 0.20, 0.35, and 0.55 μM, respectively. They were found to be better than the standard drug, geldanamycin (Hsp9 ATPase inhibition IC  = 0.90 μM). Compounds 4h and 4j with IC values of 22.82 ± 0.532, 20.78 ± 0.234 and 21.32 ± 0.765, 28.43 ± 0.653 µM showed significantly greater potencies against the MCF-7 and HepG2 cell lines, respectively. Compound 4j showed good antioxidant activities in the DPPH test and H O assay (IC  = 20.13.23 ± 0.32 and 23.27 ± 0.32 μg/mL) when compared with the standard ascorbic acid (IC  = 19.16 ± 0.20 and 20.66 ± 1.09 μg/mL). A molecular docking study was performed to observe the binding efficiency and steric interactions of the lead moiety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ardp.201800174DOI Listing
January 2019

Cholinesterase Inhibitory Activities of Selected Halogenated Thiophene Chalcones.

Cent Nerv Syst Agents Med Chem 2019 ;19(1):67-71

Division of Drug Design and Medicinal Chemistry Research Lab, Department of Pharmaceutical Chemistry, Ahalia School of Pharmacy, Palakkad-678557, Kerala, India.

Background: Dual-acting human monoamine oxidase B (hMAO-B) and cholinesterase (ChE) inhibitors are more effective than the classic one-drug one-target therapy for Alzheimer's disease (AD).

Methods: The ChE inhibitory ability of some halogenated thiophene chalcone-based molecules known to be selective hMAO-B inhibitors was evaluated.

Results: Based on the IC50 values, the selected compounds were found to moderately inhibit ChE, with IC50 values in the range of 14-70 µM. Among the synthesised molecules, T8 and T6 showed the most potent inhibitory activity against AChE and BChE, respectively.

Conclusion: Taken together, the data revealed that T8 could be further optimized to enhance its AChE inhibitory activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1871524918666181119114016DOI Listing
November 2019
-->