Bestowal of Quinazoline Scaffold in Anticancer Drug Discovery.

BACKGROUND: Cancer is one of the major causes of human mortality worldwide. A number of existing antineoplastic medications and treatment regimens are already working in the field, and several new compounds are in different phases of clinical trials. An extensive series of anticancer drugs exist in the market, and studies suggest that these molecules are associated with different types of adverse side effects. The reduction of the cytotoxicity of drugs to normal cells is a major problem in anticancer therapy. Therefore, researchers around the globe are involved in the development of more efficient and safer anticancer drugs. The output of extensive research is that the quinazoline scaffold and its various derivatives can be explored further as a novel class of cancer chemotherapeutic agents that has already shown promising activities against different tumours. Quinazoline derivatives have already occupied a crucial place in modern medicinal chemistry. Various research has been performed on quinazoline and their derivatives for anticancer activity and pharmacological importance of this scaffold has been well established. OBJECTIVE: The aim of this review is to compile and highlight the developments concerning the anticancer activity of quinazoline derivatives as well as to suggest some new aspects of the expansion of anticancer activity of novel quinazoline derivatives as anticancer agents in the near future. METHODS: Recent literature related to quinazoline derivatives endowed with encouraging anticancer potential is reviewed. With a special focus on quinazoline moiety, this review offers a detailed account of multiple mechanisms of action of various quinazoline derivatives: inhibition of the DNA repair enzyme system, inhibition of EGFR, thymidylate enzyme inhibition and inhibitory effects for tubulin polymerization by which these derivatives have shown promising anticancer potential. RESULTS: Exhaustive literature survey indicated that quinazoline derivatives are associated with properties of inhibiting EGFR and thymidylate enzymes. It was also found to be involved in disturbing tubulin assembly. Furthermore, quinazoline derivatives have been found to inhibit critical targets such as DNA repair enzymes. These derivatives have shown significant activity against cancer. CONCLUSION: In cancer therapy, Quinazoline derivatives seems to be quite promising and act through various mechanisms that are well established. This review has shown that quinazoline derivatives can further be explored for the betterment of chemotherapy. A lot of potentials are still hidden, which demands to be discovered for upgrading quinazoline derivatives efficacy.

Phyto-Phospholipid Complexation as a Novel Drug Delivery System for Management of Cancer with Better Bioavailability: Current Perspectives and Future Prospects.

Cancer is the foremost cause of death, and it supports the need for the identification of novel anticancer drugs to improve the efficacy of current-therapy. While the synthetic anticancer drug is associated with numerous side effects. Hence the plant active or phytoconstituents are in high demand for the treatment of cancer due to minimum side effects. But the polar nature of phytoconstituents hindered the absorption of the drug and lowered the therapeutic efficacy. The plant activity incorporated into Phyto-phospholipid Complexation can enhance bioavailability and improved therapeutic efficacy. In this review article, advantages, limitation and application of Phyto-phospholipid complexes have been illustrated. The article highlights the application of Phyto-phospholipid complexes as a promising drug carrier system to treat cancer.

Understanding the Pathogenesis Involved in Parkinson's Disease and Potential Therapeutic Treatment Strategies.

A vast advancement has been made in the treatment related to central nervous system disorders especially Parkinson's disease. The development in therapeutics and a better understanding of the targets results in upsurge of many promising therapies for Parkinson's disease. Parkinson's disease is defined by neuronal degeneration and neuroinflammation and it is reported that the presence of the neurofibrillary aggregates such as Lewy bodies is considered as the marker. Along with this, it is also characterized by the presence of motor and non-motor symptoms, as seen in Parkinsonian patients. A lot of treatment options mainly focus on prophylactic measures or the symptomatic treatment of Parkinson's disease. Neuroinflammation and neurodegeneration are the point of interest which can be exploited as a new target to emphasis on Parkinson's disease. A thorough study of these targets helps in modifications of those molecules which are particularly involved in causing the neuronal degeneration and neuroinflammation in Parkinson's disease. A lot of drug regimens are available for the treatment of Parkinson's disease, although levodopa remains the choice of drug for controlling the symptoms, yet is accompanied with significant snags. It is always suggested to use other drug therapies concomitantly with levodopa. A number of significant causes and therapeutic targets for Parkinson's disease have been identified in the last decade, here an attempt was made to highlight the most significant of them. It was also found that the treatment regimen and involvement of therapies are totally dependent on individuals and can be tailored to the needs of each individual patient.

Design, Synthesis and Molecular Docking Studies of Novel Thiadiazole Analogues with Potential Antimicrobial and Antiinflammatory Activities.

BACKGROUND: Chemical modification of thiadiazole may lead to a potent therapeutic agent. In this study, biological properties of thiadiazole derivatives were evaluated by assessing their antimicrobial and anti-inflammatory activities. METHODS: A series of novel derivatives of N-(5-(1-methyl-indol-3-yl)-1,3,4-thiadiazol-2- yl)-2-(5-substitutedphenyl)-3-(phenylamino)-4,5-dihydropyrazol-1-yl) acetamide have been synthesized and evaluated for their antimicrobial activity. Anti-inflammatory activity was done using carrageenan-induced inflammation in rat paw edema model. In-silico molecular docking studies of the synthesized compounds were performed on crystal structures of Aspergillus niger, Bacillus subtilis, Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Cyclooxygenase-2 (obtained from www.rcsb.org) using GRIP batch docking method of V-life MDS 3.0 software. The structures of the newly synthesized compounds were confirmed by FT-IR, 1H-NMR, 13C-NMR and Mass spectroscopy. RESULTS: Antimicrobial and Anti-inflammatory activity study of the novel synthesized compounds were screened. Synthesized compounds having methoxy substitution on the 3rd and 4th positions of aromatic ring are utmost active amongst all the derivatives. Compounds 6d, 6i, 6j and 6l were found to possess good anti-inflammatory activity having percentage of inhibition to the extent of 46.8%, 48.1%, 49.4%, and 48.5% as compared with Diclofenac. CONCLUSION: The experimental results were further supported by molecular docking analysis describing the better interaction patterns.

Malignant fibrous histiocytoma of the conjunctiva.

Fibrous histiocytomas are mesenchymal tumours composed of cells with fibroblastic to histiocytic differentiation. They can occur in any part of the body including the orbital tissues. To date, there are 18 cases of fibrous histiocytoma arising from the corneoscleral limbus reported in the literature. Eleven of these were classified as benign, and the rest were malignant fibrous histiocytomas. Benign fibrous histiocytomas have been reported in the orbit, eyelid, episclera and conjunctiva. Malignant fibrous histiocytoma has been well described in the orbit, but rarely as a primary conjunctival tumour. The rarity of the tumour makes its diagnosis and management a challenge. Herein, the clinicopathological features of a case of malignant fibrous histiocytoma are presented and its management with wide excision and cryotherapy followed by ocular reconstruction with amniotic membrane transplant is discussed.

Functional outcomes of acrylic intraocular lenses in pediatric cataract surgery.

PURPOSE: To evaluate the functional outcomes of in-the-bag implantation of acrylic intraocular lenses (IOLs) with posterior continuous curvilinear capsulorhexis (PCCC), without PCCC, with PCCC and anterior vitrectomy, and with PCCC and optic capture in pediatric cataract surgery. SETTING: Pediatric Ophthalmology Service, Guru Nanak Eye Centre, New Delhi, India. METHODS: Forty-two eyes of 25 children were included in this prospective study. All eyes had in-the-bag implantation of an AcrySof IOL (Alcon). Twenty-five eyes had had an anterior continuous curvilinear capsulorhexis (ACCC) (Group A). Seventeen eyes had PCCC along with ACCC (Group B), 4 had anterior vitrectomy combined with PCCC (Group C), and 6 had PCCC with IOL optic capture through the PCCC (Group D). Secondary opacification of the visual axis, visual acuity, and possible complications were observed and analyzed. RESULTS: The mean age of the patients was 78 months (range 36 to 144 months). The mean follow-up was 13 months (range 6 to 18 months). Four eyes (16%) in Group A developed visually significant posterior capsule opacification (PCO) involving the central visual axis and required secondary capsulotomy. All eyes in Groups B, C, and D had a clear visual axis at the last follow-up and did not require a secondary procedure. Minimal postoperative inflammation (ie, aqueous flare and IOL deposits ) was seen in all groups. The mean preoperative decimal best corrected visual acuity (BCVA) in Groups A, B, C, and D was 0.095, 0.055, 0.174, and 0.039, respectively. Postoperatively, the BCVA was 0.54, 0.66, 0.66, and 0.66, respectively. CONCLUSIONS: An optimal-sized ACCC followed by in-the-bag implantation of a foldable acrylic IOL helped maintain a clear visual axis by delaying the onset of PCO and leading to milder PCO. The benefits of a foldable acrylic IOL in pediatric cataract surgery can be increased by combining it with PCCC, with or without anterior vitrectomy, or with optic capture of the IOL.

Penicillium keratitis in vernal Keratoconjunctivitis.

We report a case of penicillium keratitis in vernal shield ulcer in the absence of corticosteroid use. This report illustrates super-added infection in vernal shield ulcer by an organism which is otherwise innocuous and forms a part of the normal ocular flora.